The Chlamydia trachomatis bacterial load could have impact on transmission and sequelae. This is the first study providing comparison of C. trachomatis load at 3 anatomic sites estimated by cycle quantification (Cq) values.Data from 7900 C. trachomatis-positive samples were included (2012-2018). Cq value was used as an inversely proportional measure for C. trachomatis load. Multivariable linear regression analyses assessed differences in mean Cq values.Vaginal swabs had the lowest Cq values (31.0) followed by urine (32.5), anorectal swabs (34.0), and oropharyngeal swabs (36.8) (P < .001). Men and women had similar oropharyngeal (36.4 vs 37.3; P = .13) and anorectal (34.2 vs 33.9; P = .19) Cq values. Men (32.2) and women (30.7) aged <25 years had lower urogenital Cq values than men (32.8) and women (31.9) aged ≥25 years (P < .001). HIV-positive patients had higher urogenital Cq values than HIV-negative patients (33.8 vs 32.6; P < .03).Men and women have a similar C. trachomatis load at extragenital locations arguing for similar transmission potential and clinical relevance. Older patients and HIV-coinfected patients had lower C. trachomatis load, suggesting exposure to previous C. trachomatis infections potentially leading to partial immunity reducing load.
The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population.
Objective
To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms.
Design, Setting, and Participants
A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk.
Intervention
Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy.
Main Outcomes and Measures
The area under the curve (AUC) for the ratio of N-terminal pro–brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy.
Results
Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08;P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non–life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%];P = .04), there were no observed safety concerns.
Conclusions and Relevance
The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels.
In recent decades, minimally invasive surgery has become the favoured surgical technique, with increasing utilisation of robotic surgery to enhance patient outcomes. However, the design complexity of surgical robotic instruments can pose challenges in maintaining adequate cleaning, disinfection and sterilisation—particularly of the device’s interior. In our hospital, robotic instruments are reused for a maximum of ten successive patients, following the manufacturer’s guidelines. To the best of our knowledge, neither the manufacturer nor ISO standards have specified any methods to determine the sterility of robotic instruments after cleaning, disinfection and sterilisation procedures. In a small pilot study, we used a locally developed protocol to evaluate the sterility of 20 da Vinci SI robotic instruments, with the aim of determining whether the recommended cleaning, disinfection and sterilisation process is adequate to achieve safe usage in subsequent patients. None of the 20 instruments showed viable micro-organisms, therefore the robotic instruments were considered sterile, and suitable for re-use. We recommend our protocol to other hospitals, to be used as an essential control element in the assessment of their unique reprocessing technique for robotic instruments.
Treponema pallidum subsp. pallidum is a fastidious spirochete and the etiologic agent of syphilis, a sexually transmitted infection (STI). Syphilis diagnoses and disease staging are based on clinical findings and serologic testing. Moreover, according to most international guidelines, PCR analysis of swab samples from genital ulcers is included in the screening algorithm where possible. It has been suggested that PCR might be omitted from the screening algorithm due to low added value. As an alternative to PCR, IgM serology might be used. In this study, we wanted to establish the added value of PCR and IgM serology for diagnosing primary syphilis. Added value was defined as finding more cases of syphilis, preventing overtreatment, or limiting the extent of partner notification to more recent partners. We found that both PCR and IgM immunoblotting could aid the timely diagnosis of early syphilis in ~24% to 27% of patients. PCR has the greatest sensitivity and can be applied to cases with an ulcer with suspected reinfection or primary infection. In the absence of lesions, the IgM immunoblot could be used. However, the IgM immunoblot has better performance in cases with suspected primary infection than in reinfections. The target population, testing algorithm, time pressures, and costs should determine whether either test provides sufficient value to be implemented in clinical practice.
Chlamydia trachomatis (chlamydia) is the most commonly diagnosed bacterial sexually transmitted infection (STI) worldwide. The advancement of molecular techniques has made chlamydia diagnostics infinitely easier. However, molecular techniques lack the information on chlamydia viability. Where in routine diagnostics the detection of chlamydia DNA or RNA might suffice, in other patient scenarios, information on the viability of chlamydia might be essential. Areas covered: In this review, the authors discuss the specific strengths and limitations of currently available methods to evaluate chlamydia viability: conventional cell culture, messenger RNA (mRNA) detection and viability-PCR (V-PCR). PubMed and Google Scholar were searched with the following terms: Chlamydia trachomatis, Treatment failure, Anal chlamydia, Microbial viability, Culture, Viability-PCR, Messenger RNA, and Molecular diagnostics Expert commentary: Several techniques are currently available to determine chlamydia viability and thus the clinical relevance of a positive test result in clinical samples. Depending on the underlying research question, all three discussed techniques have their merits when testing for viability. However, mRNA methods show the most promise in determining the presence of a true infection, in case the chlamydia reticulate body can be specifically detected. Further research is needed to understand how to best apply viability testing in current chlamydia diagnostics.
Objectives Pathogen load has been linked to disease severity in patients infected with HIV, resulting in international standards to adequately and reproducibly quantify load. Chlamydia trachomatis (CT) load has been inconsistently linked to disease severity since extensive differences exist in quantification methods (14 methods in 28 articles). Differences include normalisation for human cell load due to CT’s intracellular nature, despite the inability to distinguish inflammatory cells from epithelial cells with molecular techniques. We compared the human cell load in CT-positive men and women at the genital and anal site to a CT-negative control group to estimate the impact of inflammatory cells in these samples. Methods 188 women (tested at genital and anal site) and 519 men (207 tested at the anal site and 312 tested at the urogenital site) were included from our STI-clinic in the Netherlands. Specimens were self-collected vaginal swabs, anal swabs and urine samples. Quantitative-PCR targeting the HLA-gene quantified human cell load. Mann-Whitney-U-test was used for statistical analyses. Results The genital cell load had a similar range and median (6.5 log10) between CT-negative and CT-positive women . The urogenital cell load was significantly higher than the anal cell load (median 3.6 log10). The anal cell load was significantly higher in men with- than without anal CT infection (median 4.5 versus 3.9 respectively). The anal cell load is significantly higher in CT-positive men than in women. Both Neisseria gonorrhoeae-co-infections and reported anal intercourse significantly increased the human cell load in anal samples. Conclusion Standardisation in CT load studies is necessary as current studies show 14 different quantification methods in 28 studies . In this study we demonstrate the inappropriateness of normalising the CT load for the human cell load using molecular techniques, as the presence of inflammatory cells cannot be excluded.
Introduction Although Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection worldwide, little is known about the natural course of the bacterial load during infection. We investigated the natural course of the bacterial load in the interval between screening and returning for treatment in genital and anorectal CT-infections. Materials & Methods CT-positive patients, visiting our STI-clinic in the Netherlands from June 2011–January 2014, provided a second urogenital and/or anorectal sample when returning for treatment (diagnostic sample = T1; treatment sample = T2). Patient-record provided data about the days between samples and the date of last unsafe sex. Included patients were ≥18 years old, HIV-negative and did not report antibiotic use in the study-interval. CT load was quantified using qPCR. CT load was log-transformed, and a CT load difference (Δ-CT load) of >1 log was deemed clinically relevant. Chi-square test compared load category distributions over time (decrease/equal/increase), between sample types. Results 274 patients provided 296 paired samples. Majority of samples had a stable CT load in the interval T1-T2 (66.3%, 73.1% and 48.6% for vaginal swabs, urine and anorectal swabs resp. p = 0.07). Load decreased in 17–41% of patients, while ±10% of patients showed an increase in CT load. No association between Δ-CT load and the interval T1-T2 was observed. Large variations can be seen in CT load at T1 and over time. Discussion The majority (±90%) of patients have a stable or decreasing CT load in the time interval between screening and returning for treatment. The number of days between sampling was not associated with change in CT load. In the first month after the last unsafe sex, only stable CT loads were seen. Our data seems to indicate that when most patients visit an STI-clinic, recommended 2 weeks after infection, the infection has already been established or is in its downward phase.
Mycoplasma genitalium (MG) is associated with urethritis in men and weakly associated with pelvic inflammatory disease in women. Mycoplasma genitalium coinfections with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are commonly reported; however, little is known about their interaction. One study suggested that MG/NG coinfections might increase the bacterial load of NG, which has been shown to have a higher transmission potential. As even less is known about the impact of a simultaneous MG/CT infection, we assessed whether patients with urogenital MG/CT coinfections have a higher bacterial load than patients with a single infection.There were 1673 urogenital samples from patients from a population-based chlamydia study, and our sexually transmitted infection clinic tested for both CT and MG. When positive, the load was quantified. Nonparametric tests compared the CT and MG load, and linear regression analyses tested the association of the CT and MG load within a patient.In 60 MG-positive patients, MG load ranged from 1.7 to 6.0 log10 copies/ml, similar to the CT load distribution. Only 6 patients were MG-positive and CT-negative, but the MG load distribution was similar to that of CT-positive patients (n.s.). The MG and CT load was unrelated in coinfected persons (n.s.).We found no correlation between the CT and MG load in urogenital samples, and the MG load distribution was similar in CT-positive and CT-negative patients. These results could have implications for the transmission risk of these infections.
The goal of this multi-cohort study is to investigate the positivity rate of Trichomonas vaginalis (TV) among three distinct Dutch patient populations and its relation with Chlamydia trachomatis (CT) positivity. Few studies have been performed in Europe where TV positivity rate seems to be low. Additionally, the majority of earlier studies have focused on high risk or specific populations.A random selection of men and women from a national population-based chlamydia screening, attendees of a sexually transmitted infections (STI) clinic and a non-selected population from general practitioners (GPs) were systematically screened for TV and CT using PCR. The associations among TV and CT co-infection, age and gender were studied.A total of 2079 individuals were studied. A TV positivity rate of 1.5% was observed in the medium risk GP cohort followed by 0.7% in the low risk population-based cohort and 0.6% in the high risk STI clinic. TV was found in 0.7% of CT positives and a similar 1.1% among CT negatives. All TV positive individuals in this study were women.The positivity rate of TV was low (<2%) and comparable in all three populations studied. We found no association between TV and CT infection.
