COMPARING STIs POCTs WITH LABORATORY TESTS IN A MSM POPULATION ATTENDING A HIV/STIs CLINIC IN THE FRAMEWORK OF THE WHO ProSPeRo INITIATIVE

Despite the concerted efforts in promoting prevention and testing campaigns and the availability of highly effective treatments, HIV and other sexually transmitted infections (STIs) continue to represent a pressing public health issue worldwide. These infections disproportionally affect the so-called vulnerable populations. In Europe, the majority of HIV/STIs new diagnosis are amongst Men who have Sex with Men. Notwithstanding the rapid development of diagnostic technologies for HIV and other STIs, laboratory-based tests are not always suitable for being used both in resource-limited settings, where diagnostic access and delivery are difficult, and in high-income countries to reach the vulnerable groups. To overcome this issue, WHO endorsed the development of STIs Point-Of-Care Tests (POCTs) to tackle HIV/STIs worldwide. So far, little is known either about the STIs POCTs performance in real life setting or about the potential impact of the replacement of standard laboratory methods with the POCTs approach among different high-risk target populations. To collect robust and reliable data on those issues, in 2017 the Reproductive Health and Research (RHR) Department of WHO launched an independent evaluation on the performance of STIs POCTs among target populations called Project on Sexually Transmitted Infections Point-of-care testing established by the Reproductive Health and Research Department of WHO (ProSPeRo initiative). This thesis is to report the methodological structure and the main finding of the two studies carried out at the HIV/STIs clinic of Verona, Italy between 2017 and 2018. Considered that in the European context, and in Italy as well, the most at risk population for HIV, syphilis and gonorrhoeae is that of Men who have Sex with Men, we decided to implement the two clinical-based studies amongst them: the evaluation of the dual HIV/syphilis POCTs and that of the NG/CT POCT in genital and extragenital sites. Between May 2018 and February 2019, 492 individuals were enrolled in the HIV/Syphilis study and 300 in the NG/CT one. In the HIV/Syphilis POCT evaluation, the rapid tests yielded an almost perfect performance as far as the HIV component is concerned. As for the treponemal component, despite specificity was very high, sensitivity was found to range between 75,8 and 81,7%. In the NG/CT POCT study, the performance varied according to the anatomical site and the considered pathogen. Indeed, although specificity was found to be always above 98%, when the NG component of the POCT is taken into account, the sensitivity ranged from 75% at pharyngeal site to 87,5% at rectal and urethral site. As for the CT component of the POCT, sensitivity was 100% with pharyngeal samples and 90%, 83,3% with rectal and urethral samples, respectively. STIs POCTs are valuable tools to tackle HIV/STIs worldwide although their routinary use have to be considered in close relation with the epidemiological characteristics of the population itself, beyond the analytical characteristics of the test. The findings of this thesis support the need for independent evaluation of new diagnostic technology before being integrated in the clinical practice as well as importance of alignment of such an evaluation with the best international standards

New antibiotic development: barriers and opportunities

Antibiotic resistance represents a serious threat to public health worldwide, leading to increased healthcare costs, prolonged hospital stays, treatment failures and deaths. To address the emergency of multidrug-resistance, the major international societies of infectious diseases and public health have developed strategies and guidelines to reduce unnecessary antimicrobial use as well as to incite the development of new antibiotics targeting multidrug-resistant pathogens. Even though pharmaceutical companies have been developing new antibiotics since 2010, the global situation is still worrisome. Indeed, the currently available data regarding new antibiotics are limited to microbiological activity and pharmacokinetic profile and their use for the treatment of life-threatening infections (i.e., sepsis) is often off-label. The aim of this article is to present the antibiotic molecules recently commercialized and with which clinicians will deal quite often in next years. We describe ceftolozane/tazobactam, ceftazidime/avibactam, eravacycline, plazomicin, dalbavancin, oritavancin and tedizolid in terms of mechanism of action, antimicrobial spectrum, trials behind the approval and possible indications for the future. In last few years, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved many new antibiotic molecules but, unfortunately, they lack in biological innovation and in wide clinical indications. These agents show appealing properties for off-label use, as we propose in the article, but caution is still needed considering that high-quality clinical data are limited

Field evaluation of two point-of-care tests for syphilis among men who have sex with men, Verona, Italy

Objectives: The incidence of HIV and syphilis among men who have sex with men (MSM) in Europe has recently increased. Rapid point-of-care tests (POCTs) for syphilis can improve access to screening. The purpose of this study was to evaluate the performance of two syphilis POCTs compared with laboratory tests among MSM. Methods: The study was undertaken in Verona, Italy. Asymptomatic MSM, potentially exposed to syphilis, were enrolled prospectively. The POCTs evaluated were SD Bioline Syphilis 3.0 and Chembio DPP Syphilis Screen & Confirm Assay on both serum and fingerprick blood. The results of the POCTs were read by the naked eye by two independent readers and their concordance assessed. Results: A total of 289 MSM were enrolled in the study. Based on laboratory tests, 35 MSM (12.1%) were TPPA-positive alone and 16 (5.5%) were both Treponema pallidum particle agglutination test (TPPA) and rapid plasma reagin (RPR)-positive. The specificities of both POCTs were above 99% on both serum and fingerstick blood specimens, while sensitivities varied considerably. The sensitivity of the SD Bioline test was lower on fingerprick blood (51.4% and 54.3%, readers 1 and 2, respectively) compared with that on serum (80.0% and 82.9%). In contrast, the Chembio test exhibited similar sensitivity values for serum and fingerprick samples (57.7% and 64.0% on serum vs 65.4% and 69.2% on fingerprick for the treponemal component; 63.6% on both samples by both readers for the non-treponemal component). The positive predictive value ranged between 100% and 93.9% for the treponemal component of both syphilis POCTs, but was lower (76.3%-100%)%) for the non-treponemal component of the Chembio POCT. The negative predictive value surpassed 90% for both tests on both samples. The agreement between readers was very high (>99%). Conclusion: The diagnostic performance of the syphilis POCTs was lower than expected; however, considering the prevalence of syphilis among MSM, POCTs should be recommended to improve syphilis detection among MSM

Sexual satisfaction, an indicator of sexual health and well-being? Insights from STI/HIV prevention research in European men who have sex with men

Introduction Although sexual health has been holistically defined to include sexual satisfaction, it has been largely absent in health services and sexual and reproductive health and rights programmes in many parts of the world. We propose sexual satisfaction as a useful indicator, as one of the proxy measures for sexual health and well-being and as a component of well-being in general. Methods The Sialon II project is a multicentre biological and behavioural cross-sectional community-based survey implemented across 13 European cities during 2013–2014 among men who have sex with men. Sexual satisfaction was explored using one single item: ‘How satisfied are you with your sex life?’ A multivariable multilevel logistic random-intercept model was estimated to identify factors associated with reporting positive sexual satisfaction versus negative sexual satisfaction. Results Age, the number of partners and self-reported HIV status were not significantly associated with sexual satisfaction in the multivariate model. Participants reporting an insertive role or reported both an insertive and receptive role during the last anal intercourse were more likely to be sexually satisfied, compared with a receptive role. Participants reporting anal intercourse with a condom were more likely to be satisfied than those declaring no anal intercourse in the last 6 months, but no significant association was found compared with anal intercourse without condom. Knowledge of HIV-serostatus concordance with the last sexual partner was positively correlated with sexual satisfaction. Having had sexual intercourse with non-steady partners only in the last 6 months was negatively correlated. The more positive participants perceived their work/school, parents and friends/acquaintances’ attitudes towards gay or bisexual persons, the higher the odds they were satisfied with their sexual life. Conclusion Using a single item on sexual satisfaction in a bio-behavioural study, our analysis has shown that it is associated with individual, interpersonal and social/structural factors and has proven its usefulness as a sexual health indicator among men who have sex with men

Field evaluation of two point-of-care tests for syphilis among men who have sex with men, Verona, Italy.

OBJECTIVES: The incidence of HIV and syphilis among men who have sex with men (MSM) in Europe has recently increased. Rapid point-of-care tests (POCTs) for syphilis can improve access to screening. The purpose of this study was to evaluate the performance of two syphilis POCTs compared with laboratory tests among MSM. METHODS: The study was undertaken in Verona, Italy. Asymptomatic MSM, potentially exposed to syphilis, were enrolled prospectively. The POCTs evaluated were SD Bioline Syphilis 3.0 and Chembio DPP Syphilis Screen & Confirm Assay on both serum and fingerprick blood. The results of the POCTs were read by the naked eye by two independent readers and their concordance assessed. RESULTS: A total of 289 MSM were enrolled in the study. Based on laboratory tests, 35 MSM (12.1%) were TPPA-positive alone and 16 (5.5%) were both Treponema pallidum particle agglutination test (TPPA) and rapid plasma reagin (RPR)-positive. The specificities of both POCTs were above 99% on both serum and fingerstick blood specimens, while sensitivities varied considerably. The sensitivity of the SD Bioline test was lower on fingerprick blood (51.4% and 54.3%, readers 1 and 2, respectively) compared with that on serum (80.0% and 82.9%). In contrast, the Chembio test exhibited similar sensitivity values for serum and fingerprick samples (57.7% and 64.0% on serum vs 65.4% and 69.2% on fingerprick for the treponemal component; 63.6% on both samples by both readers for the non-treponemal component). The positive predictive value ranged between 100% and 93.9% for the treponemal component of both syphilis POCTs, but was lower (76.3%-100%)%) for the non-treponemal component of the Chembio POCT. The negative predictive value surpassed 90% for both tests on both samples. The agreement between readers was very high (>99%). CONCLUSION: The diagnostic performance of the syphilis POCTs was lower than expected; however, considering the prevalence of syphilis among MSM, POCTs should be recommended to improve syphilis detection among MSM

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 amongst keypopulations and vulnerable populations using tests detecting treponemal and nontreponemalantibodies. Whilst treponemal tests have high sensitivities and specificities,they differ regarding subjective or objective interpretation, throughput and workload.CLIAs are cost- and time-effective automated methods for detecting treponemalantibodies. The TPPA has been considered the “gold standard” treponemal assay,however, this includes a highly manual procedure, low throughput and subjectiveinterpretation. The present multi-country study evaluated the ADVIA Centaur® SyphilisCLIA assay compared to the reference SERODIA-TP·PA® for the serodiagnosis ofsyphilis amongst MSM.Method:1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a largerWHO multi-country and multi-site ProSPeRo study. Serum was tested with the CLIAassay and TP·PA, in accordance with the manufacturers’ instructions, for a first roundof validation. A second round of validation was carried out for discrepant results thatwere additionally tested with both Western Blot and an Immunoblot.Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihoodratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-testprobability were calculated.Results:Out of 1,485 eligible samples analysed in the first phase, the SERODIATP·PA identified 360 positive and 1,125 negative cases. The CLIA assay identified 366positives, missclassifying one TPPA-positive sample. In the second phase, the CLIAresulted in 1 false negative and 4 false positive results. Considering the syphilis studyprevalence of 24% (95% CI: 22-26.7), The sensitivity of the ADVIA Centaur® SyphilisCLIA 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 PPVand NPV values were above 98%Conclusions:The CLIA assay showed similar performance compared to the SERODIA-TP·PA.Considering the study is based on QUADAS principles and with a homogeneouspopulation, results are also likely to be generalisable to MSM population but potentiallynot applicable to lower prevalence populations routinely screened for syphilis. Theautomated CLIA treponemal assay confirmed to be accurate and appropriate forroutine initial syphilis screening, i.e. when the reverse testing algorithm is applied

insights from a bio-behavioural survey in thirteen cities

Publisher Copyright: © 2020 Author(s) (or their employer(s)). No commercial re-use. See rights and permissions. Published by BMJ.Objectives: This paper aims to estimate the percentage of European men who have sex with men (MSM) who may benefit from pre-exposure prophylaxis (PrEP), applying the three most widely used HIV risk indices for MSM (MSM Risk Index, Menza score, San Diego Early Test (SDET) score) and drawing on a large-scale multisite bio-behavioural survey (Sialon II). Methods: The Sialon II study was a bio-behavioural survey among MSM implemented in 13 European cities using either time-location sampling or respondent-driven sampling. Biological and behavioural data from 4901 MSM were collected. Onlybehavioural data of HIV-negative individuals were considered. Three widely used risk indices to assess HIV acquisition risk among MSM were used to estimate individual HIV risk scores and PrEP eligibility criteria. Results: 4219 HIV-negative MSM were considered. Regardless the HIV risk score used and the city, percentages of MSM eligible for PrEP were found to range between 5.19% and 73.84%. Overall, the MSM Risk Index and the Menza score yielded broadly similar percentages, whereas the SDETIndex provided estimates constantly lower across all cities. Although all the three scores correlated positively (r>0.6), their concordance was highly variable (0.01<CCC<0.62). Conclusion: Our findings showed the impact of different scoring systems on the estimation of the percentage of MSM who may benefit from PrEP in European cities. Although our primary aim was not to compare the performance of different HIV risk scores, data show that a considerable percentage of MSM in each city should be offered PrEP in order to reduce HIV infections. As PrEP is highly effective at preventing HIV among MSM, our findings provide useful, practical guidance for stakeholders in implementingPrEP at city level to tackle HIV infections in Europe.publishersversionpublishe

The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population

Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19

Standardised protocol for a prospective cross-sectional multicentre clinic-based evaluation of two dual point-of-care tests for the screening of HIV and syphilis in men who have sex with men, sex workers and pregnant women

Introduction Dual point-of-care tests (POCTs) for detecting antibodies to HIV and syphilis have been developed for use with venous whole blood, serum/plasma or finger-prick capillary whole blood. Several tests are commercially available showing encouraging performance compared with ‘gold-standard’ reference tests in laboratory-based studies. However, data on their performance in the field are limited. This prospective cross-sectional study will conduct a clinic-based evaluation to assess the performance characteristics and acceptability to end-users of two dual HIV/syphilis POCTs for the screening of HIV and syphilis among men who have sex with men (MSM), sex workers (SWs) and pregnant women (PW). This master protocol outlines the overall research approach that will be used in seven countries. Method and analysis MSM, SWs and PW presenting at clinic evaluation sites in high, low and middle-income countries will be enrolled. The (WHO preapproved) POCTs to be evaluated are SD Bioline HIV/Syphilis Duo (Abbott) and Dual Path Platform HIV-Syphilis Assay (Chembio). Finger-prick blood will be collected to perform POCTs and compared with laboratory results (venepuncture blood). Procedures will be carried out by trained healthcare staff and tests performed according to the manufacturers’ directions. Sample size was calculated based on local prevalence of HIV and syphilis. The sensitivity, specificity, positive and negative predictive values for each POCT will be calculated. The study is ongoing with recruitment expected to be completed in all countries by mid to late 2021. Ethics and dissemination This core protocol was independently peer reviewed and approved by the Research Project Review Panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The protocol has been adapted to individual countries and approved by RP2, ERC and institutional review boards at each site. Results will be disseminated through peer-reviewed journals and relevant conferences