Patrick J Horner

Performance of the Cepheid CT/NG Xpert Rapid PCR Test for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae

ABSTRACT Tests for Chlamydia trachomatis and Neisseria gonorrhoeae, which can provide results rapidly to guide therapeutic decision-making, offer patient care advantages over laboratory-based tests that require several days to provide results. We compared results from the Cepheid GeneXpert CT/NG (Xpert) assay to results from two currently approved nucleic acid amplification assays in 1,722 female and 1,387 male volunteers. Results for chlamydia in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 97.4%, 98.7%, and 97.6%, respectively, and for urine samples from males, a sensitivity of 97.5%, with all specificity estimates being ≥99.4%. Results for gonorrhea in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 100.0%, 100.0%, and 95.6%, respectively, and for urine samples from males, a sensitivity of 98.0%, with all estimates of specificity being ≥99.8%. These results indicate that this short-turnaround-time test can be used to accurately test patients and to possibly do so at the site of care, thus potentially improving chlamydia and gonorrhea control efforts.

Azithromycin antimicrobial resistance and genital Chlamydia trachomatis infection: duration of therapy may be the key to improving efficacy

A test of cure following treatment for uncomplicated cervical or urethral Chlamydia trachomatis infection with either single dose azithromycin (1 g) or doxycyline (100 mg twice daily for 7 days) is currently not recommended. Earlier trials indicated that both treatments are more than 95% effective.1–3 However, recent evidence strongly suggests that treatment failure may occur in more than 5% patients. This was the subject of a recent editorial by Handsfield4 and a late breaker symposium at the recent ISSTDR meeting in Quebec. Handsfield has argued persuasively that this apparent increase in treatment failure with azithromycin is probably not real. Tissue culture, which is less sensitive than nucleic acid amplification tests, was predominantly used in the original treatment trials and would not have been able to detect small numbers of persistent of C trachomatis bacteria.1 4 This article reviews the evidence for treatment failure, considers whether we need to modify current treatment regimes and suggests possible topics for future research. It has always been assumed that individuals retesting positive for chlamydia after a full course of treatment may be due to re-infection.2 But, azithromycin treatment failures at levels >5% where re-infection has been excluded have been documented in women, men with non-gonococcal urethritis (NGU) and in men with rectal chlamydia. Two studies in women, not at risk of re-infection, have observed treatment failure rates of approximately 8%.5–7 A high failure rate (23%) was also recently observed in men with non-gonococcal urethritis treated with single dose azithromycin who were advised to abstain from sexual intercourse.8 Although re-infection could not be excluded, the doxycycline (100 mg twice daily for 7 days) group which did not differ in terms of sexual behaviour following treatment had a significantly lower failure rate (5.2%).4 8 In a retrospective study of …

How much do delayed healthcare seeking, delayed care provision, and diversion from primary care contribute to the transmission of STIs?

Objectives: To quantify the contribution of patient delay, provider delay, and diversion between services to delayed access to genitourinary medicine (GUM) clinics. To describe the factors associated with delay, and their contribution to STI transmission. Methods: Cross-sectional survey of 3184 consecutive new patients attending four GUM clinics purposively selected from across England to represent different types of population. Patients completed a short written questionnaire that collected data on sociodemographics, access, and health-seeking behaviour. Questionnaires were then linked to routinely collected individual-level demographic and diagnostic data. Results: Patient delay is a median of 7 days, and does not vary by demographic or social characteristics, or by clinic. However, attendance at a walk-in appointment was associated with a marked reduction in patient delay and provider delay. Among symptomatics, 44.8% of men and 58.0% of women continued to have sex while awaiting treatment, with 7.0% reporting sex with >1 partner; 4.2% of symptomatic patients reported sex without using condoms with new partner(s) since their symptoms had begun. Approximately 25% of all patients had already sought or received care in general practice, and these patients experienced greater provider delay. Conclusions: Walk-in services are associated with a reduction in patient and provider delay, and should be available to all populations. Patients attending primary care require clear care pathways when referred on to GUM clinics. Health promotion should encourage symptomatic patients to seek care quickly, and to avoid sexual contact before treatment.

Risk of Pelvic Inflammatory Disease Following Chlamydia trachomatis Infection: Analysis of Prospective Studies With a Multistate Model

Our objective in this study was to estimate the probability that a Chlamydia trachomatis (CT) infection will cause an episode of clinical pelvic inflammatory disease (PID) and the reduction in such episodes among women with CT that could be achieved by annual screening. We reappraised evidence from randomized controlled trials of screening and controlled observational studies that followed untreated CT-infected and -uninfected women to measure the development of PID. Data from these studies were synthesized using a continuous-time Markov model which takes into account the competing risk of spontaneous clearance of CT. Using a 2-step piecewise homogenous Markov model that accounts for the distinction between prevalent and incident infections, we investigated the possibility that the rate of PID due to CT is greater during the period immediately following infection. The available data were compatible with both the homogenous and piecewise homogenous models. Given a homogenous model, the probability that a CT episode will cause clinical PID was 0.16 (95% credible interval (CrI): 0.06, 0.25), and annual screening would prevent 61% (95% CrI: 55, 67) of CT-related PID in women who became infected with CT. Assuming a piecewise homogenous model with a higher rate during the first 60 days, corresponding results were 0.16 (95% CrI: 0.07, 0.26) and 55% (95% CrI: 32, 72), respectively.

The role of Mycoplasma genitalium in non-gonococcal urethritis

Mycoplasmas are the smallest prokaryotes capable of self replication . Mycoplasma genitalium, one of 14 mycoplasmas of human origin known so far, was isolated originally from the urethra of two of 13 men with non-gonococcal urethritis (NGU) attending the genitourinary medicine (GUM) clinic at St Marys Hospital, Paddington, London, in 1980.1, 2 By electron microscopy, it was found to be flask shaped, the narrow terminal portion being instrumental in its attachment to eukaryotic cell surfaces.1, 2 Later, the genome of M genitalium , the smallest known for a self replicating micro-organism, 580 kb, was the first of any micro-organism to be fully sequenced.3 The small genome size probably accounts, as least in part, for the fastidious growth requirements of M genitalium . Indeed, despite the original success of isolating this mycoplasma from the urogenital tract and the subsequent recovery of five strains from the respiratory tract,4 further attempts to isolate it from the urogenital tract failed and it was not until the application of a molecular approach that progress was made. It was the advent of polymerase chain reaction (PCR) technology in the late 1980s that saw the development of sensitive and specific PCR assays for M genitalium , initially by two groups of workers and later by others, each group amplifying different fragments of the attachment protein designated MgPa.5 This has enabled M genitalium to be detected reliably in urogenital specimens. In the past 20 years there have been 19 studies,1, 6–23 undertaken largely in men attending GUM clinics, in 17 of which the relation of the mycoplasma …

Pgp3 antibody enzyme-linked immunosorbent assay, a sensitive and specific assay for seroepidemiological analysis of Chlamydia trachomatis infection.

ABSTRACT Understanding of the burden of Chlamydia trachomatis infection and its clinical sequelae is hampered by the absence of accurate, well-characterized tests using serological methods to determine past exposure to infection. An “in-house” immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) based on the C. trachomatis-specific antigen Pgp3 was produced and evaluated against three commercial ELISAs derived from the major outer membrane protein: the Medac pELISA plus, the Savyon SeroCT-IgG ELISA, and the Ani Labsystems IgG enzyme immunoassay. Sensitivities and specificities were determined using sera from both male and female patients (n = 356) for whom C. trachomatis had been detected in the lower genital tract at least 1 month prior to the testing of the sample and from 722 Chlamydia-negative children aged 2 to 13 years. The Pgp3 ELISA was significantly more sensitive (57.9% [95% confidence interval {95% CI}, 52.7 to 62.9%]) than the Ani Labsystems (49.2% [95% CI, 44.0 to 54.3%]; P = 0.003), SeroCT (47.2% [95% CI, 42.1 to 52.4%]; P < 0.0005), and Medac (44.4% [95% CI, 39.3 to 49.6%]; P < 0.0005) ELISAs. The Pgp3, Ani Labsystems, and SeroCT assays, but not the Medac assay, had significantly higher sensitivity for female specimens than for male specimens (73.8 versus 44.2%, 59.8 versus 40.5%, 55.5 versus 40%, and 45.7 versus 43.7%, respectively). For female patients, the Pgp3 assay was 14.0% (95% CI, 5.5 to 22.5%) more sensitive than the next most sensitive ELISA, the Ani Labsystems assay (P = 0.001). There was no significant difference in specificity between the Pgp3 (97.6% [95% CI, 96.2 to 98.6%]), Ani Labsystems (99% [95% CI, 97.7 to 99.6%]), SeroCT (97.2% [95% CI, 95.7 to 98.2%]), and Medac (96% [95% CI, 94.3 to 97.2%]) ELISAs. None of the ELISAs showed evidence of cross-reactivity with antibodies to Chlamydia pneumoniae.

A Novel Bacterial Mucinase, Glycosulfatase, Is Associated with Bacterial Vaginosis

ABSTRACT The modifications to the vaginal habitat accompanying a change to vaginal flora in bacterial vaginosis (BV) are poorly understood. In this study enzymes involved in mucin degradation were measured, including a novel glycosulfatase assay. Women attending an emergency walk-in sexually transmitted disease clinic were studied. One high vaginal swab (HVS) was used to prepare a gram-stained smear to determine BV status, using Ison and Hays criteria, and a separate swab was used for the purposes of the assays. The median glycosulfatase activity was 8.5 (range, −1.2 to 31.9) nmol h−1 1.5 ml−1 of HVS suspension in patients with BV compared to 0.5 (range, −0.7 to 9.4) nmol h−1 1.5 ml−1 of HVS suspension in patients without BV (P = <0.001). The median glycoprotein sialidase activity was 29.2 (range, −17 to 190) nmol h−1 1.5 ml−1 of HVS suspension in patients with BV compared to −1.1 (range, −41 to 48) nmol h−1 1.5 ml−1 of HVS suspension in patients without BV (P < 0.001). A rapid spot test for sialidase was positive in 22/24 patients with BV (sensitivity, 91.7%; 95% confidence interval [CI], 73 to 99%) and negative in 32/35 patients without BV (specificity, 91.4%; 95% CI, 76.9 to 98.2%) (P < 0.001). Glycosulfatase activity significantly correlated with both glycoprotein sialidase activity and the sialidase spot test (P = 0.006 and P < 0.001, respectively). The results are consistent with the hypothesis that the consortium of bacteria present in BV requires the ability to break down mucins in order to colonize the vagina and replace the normal lactobacilli.

Costs and cost effectiveness of different strategies for chlamydia screening and partner notification: an economic and mathematical modelling study

Objectives To compare the cost, cost effectiveness, and sex equity of different intervention strategies within the English National Chlamydia Screening Programme. To develop a tool for calculating cost effectiveness of chlamydia control programmes at a local, national, or international level. Design An economic and mathematical modelling study with cost effectiveness analysis. Costs were restricted to those of screening and partner notification from the perspective of the NHS and excluded patient costs, the costs of reinfection, and costs of complications arising from initial infection. Setting England. Population Individuals eligible for the National Chlamydia Screening Programme. Main outcome measures Cost effectiveness of National Chlamydia Screening Programme in 2008–9 (as cost per individual tested, cost per positive diagnosis, total cost of screening, number screened, number infected, sex ratio of those tested and treated). Comparison of baseline programme with two different interventions—(i) increased coverage of primary screening in men and (ii) increased efficacy of partner notification. Results In 2008–9 screening was estimated to cost about £46.3m in total and £506 per infection treated. Provision for partner notification within the screening programme cost between £9 and £27 per index case, excluding treatment and testing. The model results suggest that increasing male screening coverage from 8% (baseline value) to 24% (to match female coverage) would cost an extra £22.9m and increase the cost per infection treated to £528. In contrast, increasing partner notification efficacy from 0.4 (baseline value) to 0.8 partners per index case would cost an extra £3.3m and would reduce the cost per infection diagnosed to £449. Increasing screening coverage to 24% in men would cost over six times as much as increasing partner notification to 0.8 but only treat twice as many additional infections. Conclusions In the English National Chlamydia Screening Programme increasing the effectiveness of partner notification is likely to cost less than increasing male coverage but also improve the ratio of women to men diagnosed. Further evaluation of the cost effectiveness of partner notification and screening is urgently needed. The spreadsheet tool developed in this study can be easily modified for use in other settings to evaluate chlamydia control programmes.

Association of Mycoplasma genitalium with balanoposthitis in men with non-gonococcal urethritis

Objective To determine whether Mycoplasma genitalium is associated with balanitis and/or posthitis in a previous study of the role of M genitalium in men with acute non-gonococcal urethritis (NGU). Methods In a previous study of men with acute NGU, the existence of balanitis and/or posthitis was recorded. Chlamydia trachomatis, M genitalium and ureaplasmas were sought in urethral swabs and urine using a direct fluorescent antibody test and in-house PCR, an in-house PCR and a culture method, respectively. Men were treated with doxycycline or erythromycin. Results M genitalium was associated significantly (p=0.01) with balanitis and/or posthitis in 114 men with acute NGU. This association persisted when there was control for C trachomatis and urethral discharge (p=0.021, OR 4.1, 95% CI 1.2 to 13.5). C trachomatis and ureaplasmas were not associated with balanitis and/or posthitis. Conclusion Detection of M genitalium in men with acute NGU was associated significantly with balanitis and/or posthitis. The association is biologically plausible and may have a role in HIV-1 transmission and susceptibility.

2016 European guideline on the management of non-gonococcal urethritis.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.