Open Forum Infectious Diseases最新文献

Background: The nationwide Treatment as Prevention program for Hepatitis C (TraP HepC) was initiated in Iceland in 2016, where direct-acting antivirals (DAAs) replaced interferon-based treatments for hepatitis C virus (HCV). The study aimed to assess the impact of TraP HepC on the epidemiology of HIV/HCV coinfection, the cascade of care, and HCV reinfection rates among coinfected individuals.

Methods: A nationwide retrospective study was conducted on all people with HIV in Iceland who tested HCV antibody positive during 2000-2020. Medical records, laboratory results, and treatment outcomes were reviewed and analyzed by treatment era: interferon (2000-2015) and DAA (2016-2020).

Results: Out of 648 people with HIV, 78 were HCV antibody positive during 2000-2020, of whom 61 had confirmed HCV viremia. The total number of HIV/HCV-coinfected individuals increased steadily, peaking at 41 in 2016, but decreased by >85% to 6 by 2020 following the nationwide TraP HepC program. In total, 84 active HCV infections including reinfections were diagnosed, which prompted 81 treatment initiations and yielded 66 cures. During the interferon era, 45% (13/29) achieved cure, compared with 88% (53/60; P < .001) in the DAA era. The HCV reinfection rate in this group was 9.35/100 person-years, all presumed to be acquired by injection drug use.

Conclusions: Before the nationwide elimination campaign, the incidence of HIV/HCV coinfections was steadily increasing, but it has subsequently decreased by >85%, primarily due to the widespread use of DAAs. However, high reinfection rates in this population suggest that ongoing prevention, early diagnosis, and easy access to DAAs are necessary to maintain success.

Background: Influenza virus infection remains a major cause of morbidity in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Vaccination is a key preventive strategy; yet, clinical evidence of its benefit in this population is limited.

Methods: We conducted a retrospective, multicenter observational study including adult allo-HCT recipients (≥16 years) who developed laboratory-confirmed influenza infection between 2013 and 2023, with the aim of assessing the impact of vaccination on influenza disease severity. Vaccinated status was defined as having received the seasonal influenza vaccine during the same season and before the onset of influenza infection.

Results: A total of 143 recipients with 214 influenza episodes were analyzed. The median age was 45 years (range 18-70), and 58% had acute leukemia or myeloid malignancies. Most (64.3%) received transplants from unrelated or haploidentical family donors. Overall, 48 episodes (22%) occurred after influenza vaccination. At infection onset, 52% of vaccinated recipients were profoundly immunosuppressed (within <6 months post-transplant, experiencing active graft-versus-host disease, or receiving immunosuppressors or corticosteroids). Progression to lower respiratory tract disease (LRTD) occurred in 29% of episodes. Multivariable analysis showed influenza vaccination was significantly associated with reduced LRTD risk (HR 0.18; 95% CI: 0.06-0.50; P = .001), while a high-risk immunodeficiency scoring index (ISI) (HR 4.71; 95% CI: 1.99-11.17; P = .0004) and fever at screening (HR 2.16; 95% CI: 1.51-3.08; P < .001) independently predicted higher LRTD risk. Vaccination was also associated with decreased hospitalization risk (OR 0.20; 95% CI: 0.05-0.57; P = .005); whereas, high-risk ISI was linked to higher admission risk (OR 22.86; 95% CI: 4.82-170, P = .0003).

Conclusions: This study provides real-world evidence that seasonal influenza vaccination may reduce disease severity in allo-HCT recipients and confirms the prognostic value of the ISI for disease risk assessment.

Background: The COVID-19 pandemic caused a global disruption in respiratory syncytial virus (RSV) epidemiology. However, data on RSV epidemiology in the postpandemic period remain limited. We analyzed shifts in RSV seasonality, age distribution, and disease severity among RSV-positive children in the Netherlands before, during, and after the pandemic.

Methods: Between May 2021 and April 2024, children under two years of age, admitted with RSV to 47 Dutch hospitals were included in a prospective surveillance study. We compared demographic and clinical characteristics of RSV-positive patients with data from the pre-COVID period (2018-2020), the COVID period and the post-COVID period (2022-2024).

Results: A total of 8457 RSV-positive cases were included, with detailed data collected from 2708 patients (13 hospitals). Following an unusual off-season shift and a period of endemic circulation, RSV seasonality has reverted to its typical prepandemic winter pattern. The median age at admission increased from 2.2 months (interquartile range [IQR]: 1.1-5.6) in the prepandemic period to 4.9 months (IQR 1.8-11.4, P < .05) during the summer outbreak (2021). This subsequently returned to prepandemic median age in the winter of 2023/2024 (2.7 months, IQR 1.3-8.0, not significant). We observed no differences in the prevalence of preterm birth or comorbidities among RSV-positive children before, during or after the COVID pandemic.

Conclusions: The COVID-19 pandemic profoundly disrupted RSV epidemiology. This prospective study demonstrates a rapid re-establishment of prepandemic patterns, including a return toward the typical age distribution during early childhood.

Background: Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral hemorrhagic fever, is characterized by high mortality rates. While neurological complications (eg, seizures, encephalitis) have been identified as adverse prognostic factors in severe cases, their association with viral replication, immune responses, and neuroinflammation remain poorly defined and urgently require systematic investigation.

Method: A cohort of 277 patients with SFTS was included and stratified based on neurological symptoms. Clinical characteristics, laboratory results, and immune markers were compared between groups.

Results: Neurological symptoms developed in 78 (28.2%) patients and were associated with significantly higher 28-day mortality. These patients had higher viral loads, elevated inflammatory cytokines (IL-6, IL-10, TNF-α, and ferritin), and more severe multi-organ dysfunction. Compared with survivors, nonsurvivors showed reduced platelet and T-cell counts, and disregulated B-cell subsets with increased plasmablasts and double-negative B cells. Viral load correlated with cytokine elevation, coagulopathy (prolonged APTT), and renal impairment (reduced eGFR). Multivariate Cox proportional hazards regression identified neurological symptoms (HR = 2.565; 95% CI: 1.641-4.011; P < .001) and viral load (HR = 1.785 per log₁₀ increase; 95% CI: 1.503-2.120; P < .001) as independent predictors of mortality.

Conclusions: Neurological manifestations and elevated viral load play a central role in the progression of SFTS and are closely associated with adverse clinical outcomes. Considering neurological symptoms and immune profiles in prognostic assessments may improve early recognition of high-risk patients and inform clinical management.

Background: Mucormycosis is a severe fungal infection that is challenging to diagnose as traditional methods lack sensitivity and serological testing is unavailable. This study aimed to evaluate the MucorGenius® PCR assay on respiratory and biopsy samples from high-risk patients with probable/proven invasive pulmonary aspergillosis (IPA), mucormycosis, or possible invasive mold infections (IMIs).

Methods: This multicenter cohort study was conducted across 4 sites in Austria, Belgium and the UK. A total of 132 respiratory and biopsy samples from 114 patients with IMI diagnosed in clinical routine (10 proven IPA, 13 proven mucormycosis, 62 probable IPA, 5 probable mucormycosis, and 35 possible IMI according to EORTC/MSGERC 2020 and FUNDICU criteria; 11 IPA/mucormycosis coinfections) were analyzed using the MucorGenius® PCR assay in ISO-certified laboratories. Results were compared with standard fungal diagnostics.

Results: Mucorales DNA was detected in 37/132 samples (28%) including 29 BAL fluids, 1 bronchial aspirate, 1 endotracheal aspirate, and 6 biopsies from 37 patients. Sensitivity was 94.4% (17/18) for detecting probable/proven mucormycosis (including 11 cases routinely diagnosed with IPA/mucormycosis coinfection). Among 72 patients with probable/proven IPA, 21 (29.2%) tested positive for Mucorales DNA, including 11 missed by routine diagnostics. Mucorales DNA was also detected in 9/35 (25.7%) of patients with possible IMI.

Conclusions: MucorGenius® PCR showed high sensitivity for detecting Mucorales and may support improved diagnosis of probable mucormycosis when included as a mycological criterion. It appears particularly valuable for identifying Aspergillus-Mucorales coinfections and detecting mucormycosis in patients with host factors, clinical or radiological evidence of IMI when routine diagnostics are negative.

Background: Licensed recombinant protein respiratory syncytial virus (RSV) vaccines can prevent substantial morbidity in older adults. However, revaccination to prevent waning protection may be suboptimal, prompting the exploration of candidates for heterologous boosting. In this clinical trial of RSV vaccine-naive older adults, we evaluated SCB-1019T, a novel unadjuvanted bivalent RSV prefusion F (preF) protein vaccine stabilized via Trimer-Tag technology, in comparison to the licensed AS01_E-adjuvanted RSV vaccine Arexvy.

Methods: In this phase 1, randomized, placebo-controlled, observer-blind study, after proof-of-concept assessments in young adults (18-59 years) and older adults (60-85 years), we administered 1 dose of SCB-1019T (n = 30), Arexvy (n = 30), or placebo (n = 10) to older adults (60-85 years). Safety, reactogenicity, and immunogenicity were assessed up to 28 days postvaccination.

Results: SCB-1019T had a more favorable local safety profile, with fewer recipients reporting injection-site reactions than Arexvy recipients (17% vs 77%), whereas systemic adverse events were similar (43% vs 50%, respectively). Injection-site reactions and systemic adverse events were mild and transient, and no safety concerns were identified for SCB-1019T or Arexvy. Importantly, SCB-1019T induced similar (∼7-fold) increases of RSV-A and RSV-B neutralizing antibody titers to Arexvy. Moreover, exploratory results indicated that SCB-1019T induced potent antibodies to 3 key neutralization epitopes.

Conclusions: In older adults, SCB-1019T had an acceptable and favorable safety profile. The humoral immunogenicity SCB-1019T was similar to that of Arexvy, which contains the potent AS01_E adjuvant. Therefore, this phase 1 study supports further development of SCB-1019T, notably in heterologous booster settings.

Mold bloodstream infections are rare but highly fatal, especially with Lomentospora prolificans and Scedosporium spp. Among 84 episodes over 20 years, the 30-day mortality rate was 38%. Cancer, intensive care unit admission, and healthcare-onset infection were linked to increased mortality rates, highlighting the need for early detection and better management strategies.

Background: With effective antiretroviral treatment, more children with perinatally acquired human immunodeficiency virus (HIV) reach adulthood. We assessed their long-term socioeconomic outcomes-educational level, reliance on social welfare or absence of income, and living in poverty-using a sibling comparison design to disentangle biological from familial and environmental influences.

Methods: We conducted a retrospective cohort study from the Netherlands using data from the ATHENA cohort and nonpublic microdata from Statistics Netherlands (CBS). We included individuals aged ≥18 years with perinatally acquired HIV and siblings without HIV (identified through maternal CBS data). Logistic regression evaluated associations between sociodemographic and HIV-related factors with outcomes. Generalized estimating equations assessed differences between groups.

Results: Among 145 individuals with HIV, 12% had low educational level, 17% relied on social welfare or had no income, and 15% lived in poverty. Receiving HIV care before 1996 was associated with low educational level (odds ratio [OR], 4.58 [95% confidence interval {CI}, 1.46-14.43]; P = .01), while older age increased odds of having no income or reliance on social welfare (OR, 1.24/year [95% CI, 1.10-1.39]; P = .0001). Older age at HIV diagnosis was linked to living in poverty (OR, 1.20/year [95% CI, 1.06-1.34]; P = .003). Compared to 94 siblings, individuals with HIV had higher odds of low education (adjusted OR [aOR], 6.59 [95% CI, 1.91-22.73]; P < .01) and having no income or social welfare reliance (aOR, 2.54 [95% CI, 1.05-6.12]; P = .04). Poverty rates did not differ significantly between groups.

Conclusions: Adults with perinatally acquired HIV face educational and economic disadvantages compared to their siblings without HIV, highlighting the lasting impact of perinatal HIV beyond familial or environmental background.

Background: Research on HDV prevalence among people with HBV/HIV coinfection in China is limited. The impact of HDV on antiretroviral therapy (ART) efficacy and liver disease progression in this population remains unclear.

Methods: This retrospective cohort study included people with HBV/HIV-1 between 2005 and 2022. Baseline plasma was tested for HDV IgM/IgG; HDV RNA was measured if antibodies were positive. Demographics, liver complications, and ART responses were compared by HDV status.

Results: Overall, 1130 people with HBV/HIV-1 were included, of whom 84 (7.4%) tested positive for HDV antibodies. Among these, 19 (22.6%) were HDV RNA-positive. Approximately 41.7% of HDV antibody-positive individuals had HCV coinfection. The median duration of ART was 7.4 years (interquartile range [IQR]: 5.1, 9.9). Longitudinal samples were available from 14 individuals with HDV RNA positivity. Baseline HDV RNA was 2.98 (IQR: 2.17, 4.78) log10 IU/mL. After a rapid decline during ART, 92.8% (13/14) of individuals reached undetectable levels at 7 years. When adjusted for HCV infection, HIV and HBV virological suppression, HBsAg clearance, and immunological nonresponders were comparable between HDV antibody-positive and -negative individuals (all P > .05), and between HDV RNA-positive and -negative individuals (all P > .05). The incidence rates of newly developed cirrhosis and hepatocellular carcinoma were also similar.

Conclusions: HDV coinfection was observed in 7.4% of people with HBV/HIV-1, as a defective virus reliant on HBV, HDV RNA declined rapidly during long-term ART and HDV coinfection did not compromise HIV or HBV treatment efficacy.

Artificial intelligence (AI) is rapidly transforming healthcare, with agentic AI systems positioned to perceive, reason, and act within clinical environments. For infectious diseases (ID) clinicians, agentic AI presents both opportunity and imperative; to embrace AI literacy and remain actively engaged in shaping their design rather than becoming passive adopters in clinical care, antimicrobial stewardship, and infection control. Historical examples show that professions failing to adapt to automation faced challenges, highlighting the urgency for ID specialists to understand AI's evolving role. While AI can streamline documentation, surveillance, and decision support, clinicians must advocate for high-quality data, define appropriate automation boundaries, and ensure human oversight in critical decisions. ID communities should lead efforts to educate clinicians, establish AI governance policies in ID operational practices, and foster interdisciplinary collaboration to guide responsible AI integration. AI literacy is the "no-regret" investment that will enable clinicians to lead this transformation-ensuring that AI supports, augments, and, when appropriate, automates the repetitive, searchable, and time-consuming tasks. The future of ID practice will be defined by how effectively clinicians leverage AI to enhance care, promote equitable access, and reclaim time for the human dimensions of medicine.