Patient Biochemistry and Treatment Need in Chronic Hepatitis B Virus Infection Across Three Continents: Retrospective Cross-Sectional Cohort Studies.

INTRODUCTION: Chronic hepatitis B virus (HBV) infection is associated with significant global morbidity and mortality. Low treatment rates are observed in patients living with HBV; the reasons for this are unclear. This study sought to describe patients' demographic, clinical and biochemical characteristics across three continents and their associated treatment need. METHODS: This retrospective cross-sectional post hoc analysis of real-world data used four large electronic databases from the United States, United Kingdom and China (specifically Hong Kong and Fuzhou). Patients were identified by first evidence of chronic HBV infection in a given year (their index date) and characterized. An algorithm was designed and applied, wherein patients were categorized as treated, untreated but indicated for treatment and untreated and not indicated for treatment based on treatment status and demographic, clinical, biochemical and virological characteristics (age; evidence of fibrosis/cirrhosis; alanine aminotransferase [ALT] levels, HCV/HIV coinfection and HBV virology markers). RESULTS: In total, 12,614 US patients, 503 UK patients, 34,135 patients from Hong Kong and 21,614 from Fuzhou were included. Adults (99.4%) and males (59.0%) predominated. Overall, 34.5% of patients were treated at index (range 15.9-49.6%), with nucleos(t)ide analogue monotherapy most commonly prescribed. The proportion of untreated-but-indicated patients ranged from 12.9% in Hong Kong to 18.2% in the UK; almost two-thirds of these patients (range 61.3-66.7%) had evidence of fibrosis/cirrhosis. A quarter (25.3%) of untreated-but-indicated patients were aged ≥ 65 years. CONCLUSION: This large real-world dataset demonstrates that chronic hepatitis B infection remains a global health concern; despite the availability of effective suppressive therapy, a considerable proportion of predominantly adult patients apparently indicated for treatment are currently untreated, including many patients with fibrosis/cirrhosis. Causes of disparity in treatment status warrant further investigation.

British Association for Sexual Health and HIV (BASHH) United Kingdom national guideline on the management of Trichomonas vaginalis 2021.

The main objective of this guideline is to assist practitioners in managing individuals diagnosed with Trichomonas vaginalis (TV). It offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of TV. It covers the management of the initial presentation, as well as how to prevent transmission and future re-infection. It is aimed primarily at people aged 16 years or older presenting to health care professionals, working in departments offering specialist care in sexually transmitted infection (STI) management within the United Kingdom. However, the principles of the recommendations are applicable across all levels of STI care providers (N.B. non-specialist services may need to develop, where appropriate, local care pathways).

Immune Profiling Demonstrates a Common Immune Signature of Delayed Acquired Immunodeficiency in Patients With Various Etiologies of Severe Injury.

OBJECTIVES: The host response plays a central role in the pathophysiology of sepsis and severe injuries. So far, no study has comprehensively described the overtime changes of the injury-induced immune profile in a large cohort of critically ill patients with different etiologies. DESIGN: Prospective observational cohort study. SETTING: Adult ICU in a University Hospital in Lyon, France. PATIENTS: Three hundred fifty-three septic, trauma, and surgical patients and 175 healthy volunteers were included in the REAnimation Low Immune Status Marker study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Extensive immune profiling was performed by assessing cellular phenotypes and functions, protein, and messenger RNA levels at days 1-2, 3-4, and 5-7 after inclusion using a panel of 30 standardized immune markers. Using this immunomonitoring panel, no specificity in the immune profile was observed among septic, trauma, and surgical patients. This common injury-induced immune response was characterized by an initial adaptive (i.e., physiologic) response engaging all constituents of the immune system (pro- and anti-inflammatory cytokine releases, and innate and adaptive immune responses) but not associated with increased risk of secondary infections. In contrary, the persistence in a subgroup of patients of profound immune alterations at the end of the first week after admission was associated with increased risk of secondary infections independently of exposure to invasive devices. The combined monitoring of markers of pro-/anti-inflammatory, innate, and adaptive immune responses allowed a better enrichment of patients with risk of secondary infections in the selected population. CONCLUSIONS: Using REAnimation Low Immune Status Marker immunomonitoring panel, we detected delayed injury-acquired immunodeficiency in a subgroup of severely injured patients independently of primary disease. Critically ill patients' immune status could be captured through the combined monitoring of a common panel of complementary markers of pro-/anti-inflammatory, innate, and adaptive immune responses. Such immune monitoring needs to be incorporated in larger study cohorts with more extensive immune surveillance to develop specific hypothesis allowing for identification of biological systems affecting altered immune function related to late infection in the setting of acute systemic injury.

Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab.

BACKGROUND: Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease. METHODS: In this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization. RESULTS: In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P = 0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively). CONCLUSIONS: Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. (Funded by Vir Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number, NCT04545060.).

An evaluation study of the Becton-Dickinson ProbeTec Qx (BDQx) Trichomonas vaginalis trichomoniasis molecular diagnostic test in two large, urban STD services.

OBJECTIVES: The BASHH guidelines recommend molecular tests to aid diagnosis of Trichomonas vaginalis (TV) infection; however many clinics continue to use relatively insensitive techniques (pH, wet-prep microscopy (WPM) and culture). Our objectives were to establish a laboratory pathway for TV testing with the Becton-Dickinson Qx (BDQx) molecular assay, to determine TV prevalence and to identify variables associated with TV detection. METHODS: A prospective study of 901 women attending two urban sexual health services for STI testing was conducted. Women were offered TV BDQx testing in addition to standard of care. Data collected were demographics, symptoms, results of near-patient tests and BDQx results for TV, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). Women with any positive TV result were treated and followed up for test of cure (TOC). RESULTS: 901 women had a TV BDQx test. 472 (53%) were white, 143 (16%) black and 499 (55%) were symptomatic. Infections detected by BDQx were: 11 TV (1.2%), three GC (0.3%) and 44 CT (4.9%). Of the 11 BDQx-detected TV infections, 8 (73%) were in patients of black ethnicity. Of these, four of seven cases (57%) were WPM-positive. All patients received treatment and nine of nine (100%) were BDQx-negative at TOC. In univariate analysis, only black ethnicity was associated with likelihood of a positive TV BDQx result (relative risk (RR) 10.2 (95% CI 2.15 to 48.4)). CONCLUSIONS: The use of the BDQ enhanced detection of TV in asymptomatic and symptomatic populations. Cost-effective implementation of the test will rely on further work to reliably detect demographic and clinical variables that predict positivity.

Syphilis: presentations in general medicine.

Syphilis is caused by the spirochete bacteriumTreponema pallidumand can be transmitted both sexually and from mother to child.T pallidumcan infect any organ and produces a clinical disease with a relapsing and remitting course. It is not hard to see, therefore, why it is often described as the great mimic. In this review, we provide an update of modern syphilis epidemiology, clinical presentations, and testing and treatment strategies.

Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

Syphilis testing, typing, and treatment follow-up: a new era for an old disease.

PURPOSE OF REVIEW: The past 15 years have seen a dramatic increase in syphilis diagnoses in several regions including China, North America, Western Europe and Australia. Worldwide, the disease remains prevalent, contributing to substantial adult morbidity and neonatal mortality. Testing and treatment strategies are largely informed by data from the early antibiotic era, but increasing use of molecular diagnostics and new screening strategies could improve the management of syphilis substantially. RECENT FINDINGS: The review explores new testing strategies for syphilis, including the importance of screening test selection and advances in point-of-care diagnostics. It then examines molecular studies of Treponema pallidum, covering typing; macrolide resistance; association between genotype and phenotype and the use of PCR in testing and monitoring strategies. SUMMARY: Clinicians should be aware of testing strategies employed by their laboratories to ensure optimal sensitivity and specificity. Locally available T. pallidum PCR assays may improve the diagnosis of early disease and inform antibiotic choice. Robust serologic follow-up is still required, but predictors of potential treatment failure, including PCR-measured bacterial load, have been identified. Re-treatment should be considered for patients in the serofast state. The publication of T. pallidum genomes would allow further and more detailed study of strains and disease pathogenesis.

Impact of HIV-1 infection on the clinical presentation of syphilis in men who have sex with men.

Men who have sex with men (MSM), especially those with HIV-1 infection, are disproportionately affected by syphilis in higher income countries. The course, and some of the clinical features of the disease, especially the development of neurosyphilis, can be affected by HIV-1 co-infection. This review documents potential differences in the clinical features of syphilis in HIV-1 infected and uninfected MSM and highlights the importance of a thorough examination and high index of suspicion when seeing and treating MSM at risk of sexually transmissible infections.

Service impact of a change in HIV-1 viral load quantification assay.

INTRODUCTION: Due to discontinuation of the Siemens Versant HIV-1 RNA (bDNA) assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV-1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut-off of 20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory demonstrated previously that a significant proportion (18%) of patients undetectable using bDNA HIV-1 RNA quantification exhibited low level viraemia (LLV) using the new assay. Local guidelines recommend that patients stable on therapy receive twice-yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service. METHODS: A retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed by ≥ one low-level (<400 copies/mL) VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC) were recorded. Patients were identified using laboratory data and information collected from electronic patient records. RESULTS were analyzed with SPSS v18. RESULTS: One hundred and ninety patients were included. DEMOGRAPHICS: 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current treatment regimens were 43.3% PI-based; 43.3% NNRTI-based and 13.7% other. Patients were stratified into VL 20-49 copies/mL (n=109); VL 50-199 copies/mL (n=71) and VL 200-399 copies/mL (n=10). In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV-1 genotype requests and 16 VC discussions (Table 1). Longer duration on HAART was associated with reduced frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18-2.21); NNRTI 0.507 (95% CI 0.30-0.85) and other 1.09 (95% CI 0.48-2.43). CONCLUSIONS: Changes in assay can result in difficulties in interpretation of patient results. The assay switch in our service had significant impact on patient and staff time and cost with an increase in patient recalls; increased frequency of VL measurement, genotypes and discussions in VC. Choice of assay is paramount to running an efficient and cost-effective clinical service.

High prevalence of macrolide resistant Treponema pallidum strains in a London centre.

OBJECTIVES: Macrolide resistant Treponema pallidum strains, caused by mutations in the 23S ribosomal RNA (23S rRNA) gene, are widespread and increasingly prevalent. The authors aimed to establish the strain types of T pallidum isolated from patients in a London sexual health centre and to determine the frequency of macrolide resistance. METHODS: T pallidum DNA from blood and ulcer samples were subjected to strain typing and mutation analysis using previously described methods. RESULTS: 18 samples were tested and a 23S rRNA point mutation conferring macrolide resistance was found in 66.6%. All resistant strains were collected from men who have sex with men and both the A2058G and the A2059G mutations were found. Two strain types were identified (14d/g and 14d/f); the predominant strain type was 14d/g and an association was noted between tp0548 type g and macrolide resistance. CONCLUSIONS: High levels of T pallidum macrolide resistance are present in London, UK, and this has clear implications for national treatment guidelines.

Getting the measure of syphilis: qPCR to better understand early infection.

OBJECTIVES: Until recently, PCR had been used to detect but not quantify Treponema pallidum. To understand infection kinetics of this uncultivable organism, a real-time PCR assay was developed to quantify 47 kDa membrane lipoprotein gene DNA (tpp47). METHODS: Assay specificity was determined against DNA from humans, skin organisms and sexually transmitted pathogens. tpp47 DNA (Nichols strain) was used to construct a standard curve for T pallidum quantification. Blood and ulcer samples were obtained from 99 patients being investigated or screened for syphilis and tpp47 was quantified. RESULTS: The assay was specific, not cross-reactive with other organisms tested and sensitive, with a detection limit of a single copy of tpp47 DNA. For ulcer samples, the assay was 100% sensitive and 97.14% specific. Sensitivity fell to 34.1% for blood samples but specificity remained high (100%). tpp47 DNA was more commonly detected, and at a higher copy number, in blood of patients with secondary infection (sensitivity 57.89%) compared with primary infection. Quantity of tpp47 DNA was higher in primary infection ulcers, especially in HIV-1-positive patients, than in ulcers persisting into secondary disease. CONCLUSIONS: Quantifying T pallidum provides insight into syphilis infection kinetics: Ulcers of primary disease in HIV-1-positive patients are perhaps more infectious and the presence and load of T pallidum bacteraemia is variable, with a peak in the secondary stage. Quantitative PCR has the potential to map T pallidum infection and to highlight the impact of HIV on syphilis.

Corneal perforation requiring corneal grafting: a rare complication of gonococcal eye infection.

The authors present a case of severe gonococcal conjunctivitis associated with corneal perforation of the right eye in a 25-year-old homosexual man. Inpatient management and corneal grafting were required. The authors demonstrate that Neisseria gonorrhoea should be considered in the presence of purulent conjunctival discharge with a white patch on the cornea or reduced vision. Regardless of whether a patient has genital symptoms, they should be referred urgently to an ophthalmologist to ensure adequate treatment of this rare but sight-threatening complication.