A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay.

INTRODUCTION: International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the "gold standard" treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM). METHOD: 1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers' instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics). Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated. RESULTS: Out of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22-26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5-100), and the specificity was 99.4% (95% CI: 98.7-99.7). The ROC area values were 0.996 (95% CI: 0.992-0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1-99.2; NPV 99.9%, 95% CI: 99.5-100). CONCLUSIONS: The ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.

Independent clinic-based evaluation of dual POCTs for screening for HIV and syphilis in men who have sex with men in Italy, Malta, Peru, and the United Kingdom.

INTRODUCTION: Globally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM). METHOD AND ANALYSES: A cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites. RESULTS: Based on laboratory tests, 23.46% (n = 598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n = 901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n = 455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n = 354/584) had evidence of antibodies to T. pallidum, and of these 60.45% (n = 214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n = 1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs). CONCLUSIONS: Both the Bioline and the Chembio dual POCT for syphilis and HIV had acceptable performance, acceptability and operational characteristics amongst MSM in the PRoSPeRo network. These dual POCTs could serve as a strategic, more cost effective, patient and healthcare provider (HCP) friendly alternative to conventional testing; in clinical and other field settings, especially those in resource-limited settings.

Resistance-guided treatment of Mycoplasma genitalium infection at a UK sexual health centre.

We evaluated the ResistancePlus® MG assay in providing macrolide resistance-guided treatment (RGT) for Mycoplasma genitalium infection at a UK sexual health centre. M. genitalium-positive samples from men with urethritis and women with pelvic inflammatory disease (PID) were tested for macrolide resistance-mediating mutations (MRMMs). MRMM-positive infections were given moxifloxacin 400 mg; otherwise 2 g azithromycin (1 g single dose and then 500 mg OD) was given. Among 57 M. genitalium-positive patients (32 men and 25 women), MRMMs were detected in 41/57 (72% [95% confidence interval (95% CI) 58-83%). Thirty-two of 43 patients given RGT attended for test of cure. Treatment failure rate was significantly lower at 1/32 (3%) than 10/37 (27%) before RGT (n = 37 [men = 23 and women = 17]; p = 0.008). Treatment failure was lower in male urethritis (0/15 vs. 7/21 p = 0.027) but not in female PID. There was a trend of a shorter time to negative test of cure (TOC) in male urethritis (55.1 [95% 43.7-66.4] vs. 85.1 [95% CI CI 64.1-106.0] days, p = 0.077) but not in female PID. Macrolide resistance is higher than previous UK reports and higher than expected. RGT reduces overall treatment failure and is particularly beneficial in M. genitalium urethritis. Fluoroquinolone resistance will continue to rise with increasing fluoroquinolone use, and RGT is critical to direct appropriate azithromycin use and prevent overuse of moxifloxacin.

Microbial contamination of powered air purifying respirators (PAPR) used by healthcare staff during the COVID-19 pandemic: an in situ microbiological study.

BACKGROUND: Powered air purifying respirators (PAPR) are an option for healthcare workers requiring respiratory protection during the current COVID-19 pandemic; they are shared between multiple people. PAPR hoods are intended for multiple uses by a single user and may pose an infection risk between wearers. METHODS: Internal components of PAPR hoods and corrugated air supply hoses were swabbed for evidence of bacterial, fungal, common respiratory viruses and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) contamination. RESULTS: Twenty-five PAPR hoods were swabbed; 10 (40%) returned positive results. Bacterial growth was detected on six PAPR; five of the PAPR tested positive for fungal growth; all tested negative for SARS-CoV-2 and common respiratory viruses. CONCLUSIONS: Bacteria and fungi can remain on internal components of PAPR hoods and air supply hoses despite following recommended disinfection procedures. PAPR hoods have the potential to act as fomites, cross-infecting wearers, and patients. Current guidelines for disinfecting PAPR hoods may not be effective for use in high risk healthcare environments.

Clearance of Mycoplasma genitalium Infection With Moxifloxacin in the Presence of Quinolone Resistance-Associated Mutations.

We present 2 cases of Mycoplasma genitalium infection that were successfully treated with moxifloxacin despite the presence of quinolone resistance-associated mutations in these strains.

High rates of treatment failure for Mycoplasma genitalium among men and women attending a sexual health clinic.

BACKGROUND: Mycoplasma genitalium (Mgen) causes non-gonococcal urethritis (NGU) and is believed to cause pelvic inflammatory disease (PID). High rates of macrolide resistance are well documented globally for Mgen. In Brighton, patients with NGU and PID are tested for Mgen and test of cure (TOC) offered post-treatment. METHODS: Demographic, clinical and treatment history data were collected over a 12-month period for all Mgen-positive patients in a Brighton-based genitourinary clinic. RESULTS: There were 114 patients with Mgen. 18% (61/339) of men with NGU and 9% (15/160) of women with PID had Mgen. 62/114 (54%) returned for first test TOC 4 weeks after treatment. 27/62 (44%) had a positive TOC; 25/27 (92.6%) had received azithromycin first line (500 mg stat then 250 mg OD for 4 days), 1/27 (3.7%) had received moxifloxacin first line (400 mg OD for 14 days) and 1/27 (3.7%) had received doxycycline first line (100 mg BD for 7 days). 20/27 (74%) returned for a second TOC 4 weeks later. 5/20 (25%) patients were positive on second TOC; 3/5 (60%) had received azithromycin second line and 2/5 (40%) had received moxifloxacin second line. Patients were more likely to have a positive TOC if they were at risk of reinfection (9/27 positive TOC vs 3/35 negative TOC; p=0.02). Patients given moxifloxacin were more likely to have a negative TOC (1/27 positive TOC vs 9/35 negative TOC; p=0.03) than those who received other antibiotic regimens. CONCLUSIONS: Treatment failure rates for Mgen following azithromycin use are substantial, raising concerns regarding resistance. However, reinfection risk may contribute, suggesting a requirement for improved public awareness and clinician knowledge.

A colorimetric indicator-displacement assay for cysteine sensing based on a molecule-exchange mechanism.

In this study, we developed an ingenious yet effective strategy for cysteine detection. The colorimetric cysteine assay is established through an indicator displacement process, where Cu2+ and pyrocatechol violet (PV) was employed as receptor and indicator, respectively. Proof-of-concept trials demonstrated that the stronger binding affinity of Cu2+ receptor toward cysteine than PV indicator endowed our colorimetric sensor with high selectivity and excellent sensitivity as well as with a lower detection limit (4.60µM and 120µM, S/N =3) by UV-visible spectroscopy and the naked eye as the signal readout, respectively. More importantly, the proposed molecule-exchange process in the indicator displacement process could be successfully used to the fabrication of a colorimetric INHIBIT logic gate and even converted into a facile naked eye analysis through paper-based analytical devices for conveniently and reliably detecting cysteine (CySH) in practical applications.

Hepatitis C core antigen testing: a reliable, quick, and potentially cost-effective alternative to hepatitis C polymerase chain reaction in diagnosing acute hepatitis C virus infection.

Hepatitis C virus (HCV) is increasingly common among human immunodeficiency virus (HIV)-infected men who have sex with men. We evaluated the efficacy of HCV core antigen in diagnosing acute HCV in an HIV-infected cohort. Compared with HCV polymerase chain reaction, core antigen proved sensitive (100%) and specific (97.9%). As a quick, simple, and cost-effective test, it has considerable utility in screening for acute HCV.

Hepatitis E infection is an under recognized cause of acute decompensation in patients with chronic liver disease.

BACKGROUND/AIMS: We aimed to assess characteristics of patients with a positive hepatitis E virus serology with emphasis on acute on chronic liver disease. METHODS: This was a retrospective audit performed at a large teaching hospital. RESULTS: Of the 164 patients tested, 15(9.1%) had a positive serology (hepatitis E virus IgG and or IgM) of whom two also had a positive hepatitis E virus RNA. Six (42.8%) had underlying chronic liver disease and presented with deteriorating liver tests±decompensation. In one patient (16%) acute hepatitis E virus infection was the aetiology for the decompensation and in three the positive hepatitis E virus IgG was a reflection of prior subclinical infection. However, in two of the six patients with unexplained decompensation there was delay (150-270 days) in obtaining a hepatitis E virus serology, which may have resulted in a negative hepatitis E virus IgM at time of testing. CONCLUSIONS: 9.1% of patients presenting with abnormal liver tests at a large teaching hospital in south east England have a positive hepatitis E virus serology of whom 42.8% have acute on chronic liver disease. In 16% hepatitis E virus infection is the aetiology for the acute decompensation. This may be an under representation as in >30% of patients with unexplained decompensation there is considerable delay in requesting a hepatitis E virus serology.