Infectious diseases (London, England)最新文献

Background: Residual immune activation is common in people living with HIV (PWH) despite antiretroviral therapy (ART) and may be associated with HIV-specific, as well as lifestyle-related factors.

Objective: We aimed to investigate markers of immune activation and neuronal injury in PWH on ART compared with controls with similar lifestyle.

Methods: Cerebrospinal fluid (CSF) and blood were collected from 50 men who have sex with men (MSM) with HIV on ART, 50 HIV-negative MSM on preexposure prophylaxis (PrEP), and 25 HIV-negative controls without PrEP. β2-microglobulin, neopterin, and neurofilament light protein (NfL) were analyzed. Cytomegalovirus and herpes simplex virus-2 serostatus, as well as sexually transmitted bacterial infections were registered.

Results: Serum and CSF β2-microglobulin and neopterin did not differ significantly between MSM with HIV and MSM on PrEP. However, both groups had significantly higher serum levels of β2-microglobulin and neopterin compared with HIV-negative controls without PrEP. Age-adjusted CSF NfL levels were also similar in MSM with HIV and MSM on PrEP, but higher than in controls without PrEP. A recent syphilis infection was associated with increased immune activation in CSF and blood.

Conclusion: Increased levels of immune activation and neuronal injury markers were found in virologically suppressed MSM with HIV and MSM on PrEP compared with controls. These findings imply that other factors than HIV contribute to the residual immune activation and impact on neurons observed in MSM with HIV on ART, and emphasize the importance of appropriate controls with similar lifestyle in studies of biomarkers in PWH.

Background: Soluble thrombomodulin, a marker of endothelial cell injury, is released into the circulation during endothelial damage and has been observed at elevated concentrations in bacterial infections. This study aimed to investigate the correlation of thrombomodulin concentrations in plasma and sputum with disease severity and etiology in bacterial community-acquired pneumonia (CAP).

Methods: A prospective study was conducted on adults hospitalized with radiologically confirmed bacterial CAP. Plasma and sputum samples were collected upon admission, and thrombomodulin concentrations were quantified using an enzyme-linked immunosorbent assay. The study included a multivariate analysis to assess whether thrombomodulin concentrations were associated with disease severity and/or bacterial etiology.

Results: Of 111 patients with bacterial CAP, including 15 with severe CAP (as defined by the American Thoracic Society/Infectious Diseases Society of America criteria) and 63 with pneumococcal etiology, thrombomodulin was measured in plasma in all patients and in sputum in 42 patients. Elevated plasma thrombomodulin concentrations were independently associated with severe CAP. Stratification by bacterial etiology showed that higher plasma thrombomodulin concentrations were linked to severe pneumonia only in patients with pneumococcal infection. The area under the receiver operating characteristic curve for detecting severe pneumococcal CAP was 0.87. Conversely, sputum thrombomodulin concentrations showed no association with disease severity or bacterial etiology.

Conclusions: Plasma thrombomodulin is a promising biomarker for identifying severe pneumococcal CAP. Sputum thrombomodulin did not correlate with disease severity or bacterial etiology. These findings support further investigation into the diagnostic and prognostic role of plasma thrombomodulin in bacterial infections.

Background: Acute respiratory infections (ARIs) are a major global health concern, particularly for children and the elderly. Although rhinoviruses are the primary pathogens causing ARIs, their epidemiology during reduced population mobility and behavioral changes is not well understood. This study aimed to assess whether the Swedish COVID-19 measures changed the epidemiology of Rhinovirus and ARI-causing viruses other than SARS-CoV-2 in the western part of Sweden in 2020.

Methods: A total of 13,791 nasopharyngeal samples from ARI-patients were analyzed for 19 different viruses and bacteria by qPCR. Of the 3,607 samples positive for any virus, 2,018 were positive for rhinovirus (RV) and enterovirus (EV), and 106 contained adenoviruses. Among the EV/RV reactive samples, 249 strains were typed using partial sequencing of 5'UTR and 204 by VP1 or VP4-VP2.

Results: After week 12 when the interventions were implemented, most of the ARI-causing viruses were EV/RV and adenoviruses, besides SARS-CoV-2. In September-October 2020, an outbreak caused by RV-A strains predominantly infected children younger than 13 years and individuals within the age range of their parents. RV-A strains were identified in 118 of 242 (49%) RV-positive samples, followed by RV-C (36%) and RV-B (10%). Before the first wave of SARS-CoV-2, a RV-C outbreak affected all age groups.

Conclusions: This study shows that the moderate Swedish interventions against SARS-CoV-2 were more effective against the spread of ARI-causing virus among adults over 56 years than among young children. These results suggest the need for new strategies for preventing the spread of ARI pathogens like RV and EV, which cause disease in all age groups and can lead to large outbreaks.

Background: Non-β-hemolytic streptococci (NBHS) cause blood stream infections (BSI) which can be complicated by infective endocarditis (IE). To stratify the risk for IE in NBHS BSI and to guide the use of echocardiography in this condition, two risk stratification systems (RSSs), the HANDOC score (HANDOC), and the Chamat-Hedemand algorithm (CH-A) have been developed.

Objectives: To compare the sensitivity and the specificity of HANDOC and CH-A and to describe how the utilization of transesophageal echocardiography (TEE) would be affected using either HANDOC or CH-A.

Methods: A retrospective, population-based cohort study of patients with blood cultures positive for NBHS during 2018 was performed. Medical records of the included patients were studied for classification of the episodes according to HANDOC, CH-A, and the Duke-ISCVID criteria.

Results: Three hundred and twenty-five episodes of NBHS BSIs involving 308 patients were included. Twenty-one episodes (6.5%) met the Duke-ISCVID criteria for definite IE. TEE was performed in 26% of episodes. HANDOC had a sensitivity of 95% and a specificity of 73% for definite IE whereas CH-A had a sensitivity of 90% and a specificity of 63%. The CH-A outcome 'any echocardiography' had a sensitivity of 100% for definite IE, but the specificity was only 24%. In this cohort, implementation of the RSSs would lead to an increase in the utilization of TEE compared to the real-life use, both when using HANDOC (+22%) and CH-A (+60%).

Conclusion: HANDOC had the highest combined sensitivity and sensitivity for IE. The utilization of TEE would increase using these RSSs, especially the CH-A.

Background: This study aimed to assess chlamydia diagnostics in different clinic types, including internet-based self-sampling (IBSS). Furthermore, we investigated the incidence of chlamydia-associated complications.

Methods: Data on Chlamydia trachomatis (CT) testing were retrieved from six healthcare regions in the years 2016-2023 across different categories of testing facilities. National data on CT diagnostics and number of PID, ectopic pregnancy and infertility cases were obtained from Swedish health authorities.

Results: The number of CT cases detected through IBSS increased by 85% from 2016 (n = 1967) to 2023 (n = 3644) when it accounted for 43% of all cases. The proportion of CT-positive individuals of all tested persons was similar for IBSS (7.0-8.5% per year); STI clinics (8.5-9.9%) and youth clinics (9.7-10.9%). In contrast, gynaecology clinics had a low proportion of CT-positive individuals (1.8-2.3%), and primary healthcare clinics a decreasing proportion (2016: 4.8%; 2023: 3.0%). For women in Sweden aged 15-39 years, there was a 33% decrease in detected CT cases from 2008 to 2022 (1577-1048 cases/100,000 women) while PID rates decreased by 63% from 2008 to 2022 (224-83 cases/100,000 women).

Conclusions: IBSS has become the most important CT case detector in Sweden. Primary care and gynaecology clinics have low positivity rates. The decrease in PID rates may be due to generous CT testing, although other explanations are possible. Considering the low positivity rates in some clinic types and that asymptomatic CT cases have a low PID rate a reduced testing may be justified.

Background: Secondary dengue virus (DENV) infection is a known risk factor for severe clinical manifestations. Antibody-dependent enhancement of viral pathogenesis explains this phenomenon; however, the underlying mechanisms remain incompletely defined.

Objectives: To compare the frequency of hypotension, endothelial activation, systemic inflammation, and thrombocytopenia in patients with primary and secondary DENV infection.

Methods: This was a cross-sectional study among children and young adults aged 1-26 years conducted at an outpatient clinic in the Philippines. Secondary infection was defined by the presence of detectable anti-DENV IgG antibodies at presentation. Clinical data and haematologic parameters were recorded. Plasma concentration of circulating markers of endothelial activation and inflammation were quantified by Luminex^® assay.

Results: Among 244 patients (median age 9 years, 40% female), 93 (38%) were IgG positive. Secondary infection was associated with a 2.2-fold increased odds (95% CI, 1.1-4.1) of hypotension compared to primary infection. Endothelial activation, quantified using a composite index of six endothelial markers (Ang1, Ang2, sTie2, sFlt1, sICAM1, and sEndoglin), was significantly higher in secondary infection (p < 0.001). Platelet counts were lower in secondary infection (170 × 10⁹/L vs 230 × 10⁹/L, p < 0.0001). IL-10 levels were elevated in secondary infection (76 pg/mL vs 33 pg/mL, p < 0.001). Systemic inflammation, quantified using a composite index of four plasma markers (TNF, CXCL8/IL-8, CXCL10/IP-10, PCT), correlated with endothelial activation (τ = 0.39, p < 0.001) and IL-10 (τ = 0.32, p < 0.0001).

Conclusion: Endothelial activation, IL-10-mediated immune dysregulation, and platelet depletion are associated with transient vascular hyperpermeability in secondary DENV infection.

Background: The WHO hepatitis C virus (HCV) elimination goal includes achieving ≥80% treatment coverage by 2030.

Objectives: This study aims to assess Sweden's progress toward elimination by estimating national HCV treatment uptake and identifying associated factors.

Methods: This nationwide register-based study includes individuals notified with HCV infection in Sweden 1990-2022. Treatment uptake was defined as at least one dispensation of HCV treatment recorded in the Swedish Prescribed Drug Register (SPDR) by the end of 2023. As the SPDR was initiated in 2005, treatment uptake was specifically analyzed in individuals notified 2005-2022. Median time from notification to treatment was analyzed annually.

Results: Among 29,815 included individuals, 24,007 (81%) had started treatment. Among notified 2005-2022, treatment uptake was 81% (13,155/16,241) by 2022 and 85% (13,548/15,930) by 2023. Factors associated with lower odds of treatment uptake were: amphetamine use diagnosis (adjusted odds ratio 0.71; 95% confidence interval 0.60-0.83), opioid use diagnosis (0.71; 0.60-0.84), combined amphetamine/opioid use diagnoses (0.75; 0.62-0.91), other drug use diagnoses (0.70; 0.60-0.81), coinfection with hepatitis B virus (0.54; 0.39-0.76), male sex (0.73; 0.67-0.81) and ≤9 years of education (0.81; 0.70-0.94). The odds were higher in individuals aged ≥60 (1.26; 1.10-1.44) years. Median time to treatment was 2.8 months (IQR 1.7-5.6) among individuals notified in 2022.

Conclusions: Sweden has reached the WHO treatment target, with treatment uptake ≥80%. In recent years, the median time to treatment has decreased to a few months. Continued efforts are needed to maintain this progress, particularly among people who inject drugs where HCV incidence remains high.

Background: A transition from fluoroquinolones to narrow-spectrum antibiotics in male patients with acute cystitis could reduce antibiotic resistance but may increase the incidence of complications. This study aimed to evaluate risks with choosing narrow spectrum-antibiotics in male patients with acute cystitis for the subsequent risks for complications (secondary events).

Methods: This was a cohort study of all male adult residents in Region Västra Götaland, Sweden followed for eight years representing 5.3 million male person years. Male patients aged ≥18 years with acute cystitis at least once from January 2012 to December 2019 (n = 38,864) were analysed with Odds Ratio (OR) and Number Needed to Harm (NNH) for using narrow-spectrum antibiotics versus broad-spectrum fluoroquinolones to cause secondary events within 30 days.

Results: Participants suffered 58,402 acute cystitis and 13,300 secondary events. The mean age of participants was 67 years (SD 17, interquartile range 58-79). The risk of pyelonephritis was higher if treated with pivmecillinam (OR 1.3, p = 0.019, NNH 440) or nitrofurantoin (OR 1.6, p < 0.001, NNH 220) at the initial cystitis compared with fluoroquinolones. Non-serious secondary events, such as treatment failure or relapse/reinfection of acute cystitis, were more common if any antibiotic other than fluoroquinolones were prescribed (OR 1.5-2.4 and NNH 5.8-14).

Conclusions: Narrow-spectrum antibiotics for acute cystitis in male patients resulted in a very small increase in the incidence of pyelonephritis and a moderate increase in treatment failure or relapse/reinfection. In our opinion this does not motivate prescribing fluoroquinolones to all men with acute cystitis.

Introduction: Dalbavancin is a lipoglycopeptide with an exceptionally long half-life that allows simplified administration, which may be of value in long-term treatment of bone and joint infections, such as prosthetic joint infections (PJIs). The objective was to determine trough (C_min) values of dalbavancin during long-term PJI treatment according to the recommendation of the Swedish National Guidelines for Bone and Joint Infections: a loading dose of 1,500 mg on day 1 and another 1,500 mg on days 8-14, followed by day 28 administration of 1,000 mg every two weeks or 500 mg per week.

Patients/methods: Twelve patients with PJI treated with at least six doses of dalbavancin were prospectively followed up, serum samples were collected, and renal function was investigated. Dalbavancin concentrations were measured using ultra-high pressure liquid chromatography coupled with unispray tandem mass spectrometry (UHPLC-MS/MS).

Results: The median serum concentration (C_min) 14 days after the first 1,500 mg dose was 36.3 mg/L (range: 6.6-62.4 mg/L). The median trough value at the date of the last given dose (1,000 mg) after a total of 6-7 doses was 53.6 mg/L (range: 32.0-97.5 mg/L). Three patients showed a tendency towards successive accumulation of dalbavancin during treatment. None of the patients showed any significant impairment in renal function.

Conclusions: Therapeutic drug monitoring during long-term dalbavancin treatment is recommended to avoid the risk of accumulation and unnecessarily high trough levels. In many cases, such monitoring can allow the dosing interval to be extended.