{"id":1274,"date":"2017-02-28T16:45:56","date_gmt":"2017-02-28T16:45:56","guid":{"rendered":"https:\/\/blogs.bmj.com\/sti\/?p=1274"},"modified":"2017-04-05T16:04:03","modified_gmt":"2017-04-05T15:04:03","slug":"bashh-centenary-vignette-series-culture-of-the-gonococcus-some-historical-details","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/sti\/2017\/02\/28\/bashh-centenary-vignette-series-culture-of-the-gonococcus-some-historical-details\/","title":{"rendered":"BASHH Centenary Vignette series: Culture of the gonococcus \u2013 some historical details"},"content":{"rendered":"<p><span style=\"text-decoration: underline\">Culture of the gonococcus \u2013 some historical details<\/span><\/p>\n<p>The 43 year period between two BJVD articles<sup>1, 2<\/sup> incubated improvements in the diagnosis of gonorrhoea by laboratory culture. The following 47 gave birth to alternative tests (NAATs), more simple to administer, but whose automation brought loss of personnel and possibly skills: perhaps in microscopy, perhaps in laboratory culture.<\/p>\n<p>In 1927 Colonel Harrison wrote<sup>1<\/sup>: \u201c<em>There are differences of opinion as to the value of cultures in the diagnosis of gonorrhoea. Personally I think them <u>indispensable in the case of women<\/u> and often valuable in male urethritis<\/em>\u201d (my emphasis).<\/p>\n<p>Laboratory culture of <em>Neisseria gonorrhoeae<\/em> has always lacked 100% sensitivity. Sampling from multiple sites, on multiple occasions, was necessary to diagnose, to exclude, and, importantly, to monitor any advances, or fluctuations, in the efficiency of laboratory culture. The use of <em>repeated<\/em> tests to analyse the sensitivity of culture is now impossible, with the universal adoption of epidemiological treatment (before\/without diagnosis).<\/p>\n<p><!--more--><\/p>\n<p>Duncan Catterall\u2019s 1970 article<sup>2<\/sup> highlights sharp contrasts with today\u2019s practice and prevalence [my comments follow his quotes]:<\/p>\n<p><em>&#8211; \u201cA full physical examination was performed on all the patients\u2026 They were all observed for at least 3 months.\u201d<\/em><\/p>\n<p>Measurement of BP, breast examination, abdominal palpation and urinalysis were standard for all new, and rebooked patients after one year.\u00a0 We were allocated more time with individual patients, almost all of whom were prepared to return for repeat tests.<\/p>\n<p><em>&#8211; \u201cgonococci were found in 95 (31.6%) of the women\u201d<\/em><\/p>\n<p>Gonorrhoea prevalence was higher then than nowadays; the mode of UK gonorrhoea incidence occurred in the mid-1970s (fig 1). Catterall\u2019s was a consecutive series of 300 women who had attended, or been referred, because of vaginal discharge. A similar series today would be lucky to include 9, let alone 95, cases of gonorrhoea.<\/p>\n<p>&nbsp;<\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/sti\/files\/2017\/04\/STI.png\"><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1275 aligncenter\" src=\"https:\/\/blogs.bmj.com\/sti\/files\/2017\/04\/STI-300x157.png\" alt=\"\" width=\"367\" height=\"192\" srcset=\"https:\/\/blogs.bmj.com\/sti\/files\/2017\/04\/STI-300x157.png 300w, https:\/\/blogs.bmj.com\/sti\/files\/2017\/04\/STI.png 446w\" sizes=\"auto, (max-width: 367px) 100vw, 367px\" \/><\/a><\/p>\n<p>&#8211; \u201c\u2026even with a first-class cultural service, repeated examinations are needed to establish the diagnosis of gonorrhoea in women\u201d<\/p>\n<p>In the 1970s at least three sets of tests were taken on separate occasions to diagnose\/exclude gonorrhoea in women. Even with multiple sets of tests, the culture results varied significantly between Centres<strong>. \u00a0<\/strong><\/p>\n<p>The decade witnessed attempts at improving cultural sensitivity: a variety of selective but non-inhibitory mediums, often modifications of Thayer-Martin\u2019s version, gradually replaced non-selective ones. Catterall used McLeod\u2019s culture medium, with no antibiotics or antifungal agents, and diagnosed 60% of gonorrhoea at the first visit.<\/p>\n<p>A series of publications from London clinics<sup>3<\/sup> demonstrated laboratory culture\u2019s <em>lack<\/em> of sensitivity but its gradual improvement. Results from the <em>first<\/em> set of tests at various Centres included 66% (Middlesex, 1970<sup>2<\/sup>), 90% (St Thomas\u2019, 1971<sup>4<\/sup>), 91% (Middlesex, 1976<sup>5<\/sup>), 88% (Charing X, 1976<sup>6<\/sup>), 97% (St Thomas\u2019, 1976<sup>7<\/sup>), 98% (St Thomas\u2019, 1978<sup>8<\/sup>), 95% (Barts, 1979<sup>9<\/sup>). All of these figures came from units with a particular interest in gonorrhoea and its diagnosis, but variation persisted.<\/p>\n<p><em>&#8211; \u201cEvery patient had at least 4 pelvic examinations and the majority had 6 or more genital tests.\u201d \u00a0<\/em><\/p>\n<p>Exclusion was as important as diagnosis. We knew that the first set of tests would miss some cases but we also knew that a number of gonorrhoea contacts would<em> not <\/em>have the disease, between 8% and 35%<sup> 10<\/sup> (polarising views for and against epidemiological treatment).\u00a0 The same may be true today: Turner writes<sup>11<\/sup> \u201c<em>Presumptive or epidemiological treatment of chlamydia and\/or gonorrhoea accounts for a large number of suboptimal and unnecessary antibiotic <\/em>prescriptions\u201d, calculating (\u201c<em>a conservative assumption<\/em>\u201d) the probability of partner infection as 0.4.<\/p>\n<p><em>&#8211; \u201cgonococci were found <\/em>[by microscopy]<em> in only 67 (69%) of 95 consecutive cases\u201d <\/em><\/p>\n<p>This last quotation demonstrates how \u2018<em>a poor culture service flatters the microscopist<\/em><sup>12<\/sup><em>\u2019<\/em>: Suppose 50 of 100 genuine cases of gonorrhoea (50%) are identified by microscopy. If culture misses 20, microscopy will appear more sensitive, at 50 of 80 (62.5%). The same calculation applies to assessment of NAATs.<\/p>\n<p>Microscopy in women at St Thomas\u2019s found 50% compared with Catterall\u2019s 69%, and a later retrospective survey<sup>13<\/sup>, from Catterall\u2019s unit, noted the poorer sensitivity of culture in small clinics outside London.\u00a0 Again variation.<\/p>\n<p>Use of Ian Phillips\u2019 VCNT<sup>4<\/sup> combined with scrupulous attention to detail, had improved culture sensitivity to 98% by 1978 (continuing at 97% in 1988<sup>14<\/sup>).<\/p>\n<p>Which brings me to the big question: how does the standard and variability of gonococcal culture today compare with (the best of) the 1970s? And does it matter?<\/p>\n<p>In 1977 Morton<sup>15<\/sup> wrote \u201c<em>The gonococcus is the most fastidious of organisms. It has long taxed the skill and ingenuity of bacteriologists<\/em>.\u201d The WHO, with Unemo and Ison\u2019s imprimatur (2013)<sup>16<\/sup>, updates the caution: \u201c<em>Strict sample collection, transportation, and storage are crucial to maintaining viability<\/em>\u201d, listing vital criteria: \u201c<em>Number of sampling sites, technique and swabs used for collection of specimens; conditions and duration of transportation; composition and quality of the culture medium; inoculation and incubation conditions; and reagents and techniques used for the species identification of N. gonorrhoeae<\/em>.\u201d<\/p>\n<p>In the 1970s, as now, we had Reference Laboratories, guidelines, and exhortations to quality control and yet there was still a <em>measurable<\/em> variation in outcomes of gonococcal culture between and within London\u2019s \u2018Centres of Excellence\u2019.<\/p>\n<p>Before I am overwhelmed by howls of protest from microbiologists (and epidemiologists), I wonder how many laboratories, whose \u2018culture\u2019 results provide today\u2019s comparators for epidemiological and NAAT evaluations, look, <em>have looked<\/em>, at the performance of their transport\/culture systems<sup>17, 18<\/sup>, in a similarly <em>fastidious<\/em> way?<\/p>\n<p>What proportion of clinics or testing sites these days have all the index samples plated direct in clinic on to an appropriate selective but non-inhibitory medium (made up in-house as required, not commercial<sup>18<\/sup>), and placed directly in the clinic\u2019s CO<sub>2<\/sub>\/humidity\/temperature-controlled incubator, with samples transferred to the on-site laboratory (dedicated gonorrhoea bench, dedicated gonorrhoea technician) twice daily, and with daily quality control to include correlation of microscopy of samples from the male urethra with their culture results.<\/p>\n<p>This crucial monitoring of<em> men\u2019s<\/em> samples enabled us to pick up problems with the incubators (clinic and laboratory), growth medium, a new technician on the \u2018GC\u2019 bench, or even sloppy plating-out in the clinic. If a discrepancy arose, we were aware of it in as few as 24 hours and were able to adjust our management of <em>women<\/em>, for whom culture was (and should still be) of so much greater importance.<\/p>\n<p>While matching the earlier paragraph\u2019s stringent conditions, culture in 1988 at St Thomas\u2019 still missed 3% of cases of gonorrhoea in women at the first attempt<sup>14<\/sup>.<\/p>\n<p>Nobody would disagree with the conclusion of a recent STI article<sup>19<\/sup> that: \u201c\u2026<em>the use of dual NAATs in the context of a population with low prevalence of gonorrhoea is likely to result in false positive results<\/em>\u201d, but one should also question any who assume that all the NAAT positive\/culture negative results in their series are <em>false <\/em>positives.<\/p>\n<p>I end with two cautions; one old, one new:<\/p>\n<p>Taylor and Phillips (1980): \u201c<em>We conclude that although these transport-culture media performed well if incubated immediately and examined immediately, performance was not nearly so good under conditions that mimic more closely those actually obtaining in most clinics<\/em>.\u201d<sup> 18<\/sup><\/p>\n<p>And my own (2017): \u2018<em>a poor culture service flatters the NAAT<\/em>, <em>and may distort measures of prevalence and incidence\u2019<\/em>.<\/p>\n<p>by \u00a0Dr David Barlow, Emeritus Consultant Physician<\/p>\n<p><u>References <\/u><\/p>\n<ol>\n<li>Harrison LW (Colonel) (1927) <em>Gonorrhoea<\/em>. Br.J.Vener.Dis. <strong>3<\/strong>, 24-32<\/li>\n<li>Catterall RD (1970) <em>Diagnosis of vaginal discharge<\/em>. Br.J.Vener.Dis. <strong>46<\/strong>, 122-4<\/li>\n<li>Barlow D (2007). <em>R.D.<\/em> <em>Morton Memorial Lecture<\/em>, BASSH Spring Meeting, Blackpool\u00a0<a href=\"https:\/\/www.researchgate.net\/publication\/270567127_Gonorrhoea\">https:\/\/www.researchgate.net\/publication\/270567127_Gonorrhoea<\/a>\u00a0 (slide 30)<\/li>\n<\/ol>\n<ol start=\"4\">\n<li>Thin RN, Williams IA, Nicol CS (1971). <em>Direct and delayed methods of immunofluorescent diagnosis of gonorrhoea in women<\/em>. Br.J.Vener.Dis. <strong>47<\/strong>, 27-30<\/li>\n<li>Chipperfield EJ, Catterall RD (1976). <em>Reappraisal of Gram-staining and cultural techniques for the diagnosis of gonorrhoea in women<\/em>. Br.J.Vener.Dis. <strong>52<\/strong>, 36-39<\/li>\n<li>Evans BA (1976). <em>Detection of gonorrhoea in women<\/em>. Br.J.Vener.Dis. <strong>52<\/strong>, 40-42<\/li>\n<li>David Barlow, Nayyar K, Phillips I and Barrow J (1976). <em>Diagnosis of gonorrhoea in women<\/em>. Br.J.Vener.Dis. <strong>52<\/strong>, 326-328<\/li>\n<li>David Barlow and Ian Phillips (1978). <em>Gonorrhoea in women: Diagnostic, clinical and laboratory aspects<\/em>. Lancet; <strong>i<\/strong>, 761-4<\/li>\n<li>Thin RNT and Shaw EJ (1979). <em>Diagnosis of gonorrhoea in women<\/em>. Br.J.Vener.Dis. <strong>55<\/strong>, 10-13<\/li>\n<li>Barlow D (2007). (slide 39)<\/li>\n<li>11.Turner KME, et al (2014) <em>An early evaluation of clinical and economic costs and benefits of implementing point of care NAAT tests for chlamydia trachomatis and Neisseria<\/em> <em>gonorrhoeae in genitourinary medicine clinics in England<\/em>. Sex Transm Infect; <strong>90<\/strong>:104-111<\/li>\n<\/ol>\n<ol start=\"12\">\n<li>Barlow D (2007). (Slide 32)<\/li>\n<li>Belsey EM (1983). <em>Diagnosis of gonorrhoea in women \u2013 a national survey<\/em>. Br.J.Vener.Dis. <strong>59<\/strong>, 59-62<\/li>\n<li>Mitchell S and Barlow D (1988) unpublished data<\/li>\n<li>Morton RD (1977) <em>Gonorrhoea<\/em>. W B Saunders Company Ltd, London, p 41<\/li>\n<li>Unemo M and Ison C (2013) <strong>WHO.<\/strong> <em>Laboratory diagnosis of sexually transmitted infections. Gonorrhoea.<\/em> p21-54 apps.who.int\/iris\/bitstream\/10665\/85343\/1\/9789241505840_eng.pdf<\/li>\n<\/ol>\n<ol start=\"17\">\n<li>Taylor E and Phillips I (1979). <em>Assessment of a selective medium for the isolation of Neisseria gonorrhoeae<\/em>. Br.J.Vener.Dis. <strong>55<\/strong>, 183-185<\/li>\n<li>Taylor E and Phillips I (1980). <em>Assessment of transport and isolation methods for gonococci<\/em>. Br.J.Vener.Dis. <strong>56<\/strong>, 390-393<\/li>\n<li>Mannion PK, Fairley CK, Fehler G et al (2016). <em>Trends in gonorrhoea positivity by nucleic acid amplification test versus culture among Australian heterosexual men with a low prevalence of gonorrhoea, 2007-2014<\/em>. Sex Transm Infect <em>2016; <\/em><strong><em>92<\/em><\/strong><em>:<\/em><em>625-628 <\/em><em>doi: 10.1136\/sextrans-2015-052246<\/em><\/li>\n<\/ol>\n<p><a href=\"https:\/\/blogs.bmj.com\/sti\/files\/2017\/02\/MF_BASHH_100_col_v2_72dpi-002.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-1261\" src=\"https:\/\/blogs.bmj.com\/sti\/files\/2017\/02\/MF_BASHH_100_col_v2_72dpi-002.jpg\" alt=\"\" width=\"199\" height=\"208\" \/><\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Culture of the gonococcus \u2013 some historical details The 43 year period between two BJVD articles1, 2 incubated improvements in the diagnosis of gonorrhoea by laboratory culture. The following 47 gave birth to alternative tests (NAATs), more simple to administer, but whose automation brought loss of personnel and possibly skills: perhaps in microscopy, perhaps in [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/sti\/2017\/02\/28\/bashh-centenary-vignette-series-culture-of-the-gonococcus-some-historical-details\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":192,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[16502],"tags":[],"class_list":["post-1274","post","type-post","status-publish","format-standard","hentry","category-centenary-vignette"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>BASHH Centenary Vignette series: Culture of the gonococcus \u2013 some historical details - Sexually Transmitted Infections<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/sti\/2017\/02\/28\/bashh-centenary-vignette-series-culture-of-the-gonococcus-some-historical-details\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"BASHH Centenary Vignette series: Culture of the gonococcus \u2013 some historical details - Sexually Transmitted Infections\" \/>\n<meta property=\"og:description\" content=\"Culture of the gonococcus \u2013 some historical details The 43 year period between two BJVD articles1, 2 incubated improvements in the diagnosis of gonorrhoea by laboratory culture. 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