Open Forum Infectious Diseases最新文献

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.

Background: Superinfection with the hepatitis D virus (HDV) leads to a more aggressive form of chronic hepatitis B. While around 5% of hepatitis B surface antigen (HBsAg)-positive individuals are estimated to be hepatitis B virus (HBV)-HDV dually infected globally, the time point of superinfection is unknown and repeated HDV testing is not yet supported by international guidelines. Inci-D is a post hoc analysis from 2 prospective cohorts to evaluate the HDV superinfection rate.

Method: The Inci-D cohort consists of 2 HBV cohorts of clinical meta-data and stored plasma samples or dried-blood spots (DBS) from The Gambia (Prolifica) and France.

Results: Overall, samples from 1016 HBsAg-positive individuals were analyzed (625 from The Gambia, 391 from France); the baseline HDV prevalence was 1.1% (7/625) and 2.5% (10/391), respectively. The median age (interquartile range) was 38 (32-50) years, and 63% were male. Patients in the French cohort were older (P < .001), with higher liver enzymes (P < .001), were more often hepatitis B e antigen positive (P < .001) or anti-HCV positive (P < .001), and had more advanced liver disease (P < .001). In the Gambian cohort, after a median follow-up time of 5.98 years, 14 individuals were detected to be newly HDV antibody (Ab) positive (3.85/1000 patient-years). In the French cohort, after a median follow-up time of 2.1 years, 3 individuals were newly detected to be HDV Ab positive (3.70/1000 patient-years).

Conclusions: Hepatitis Delta superinfection increases considerably in HBsAg-positive carriers in The Gambia as well as in France. These findings support consideration of repeated HDV serology testing in HBsAg-positive individuals.

Background: Antiretroviral therapy (ART) suppresses HIV replication and partially restores immune function, but immunologic abnormalities often persist.

Methods: We performed longitudinal multiparametric flow cytometry on peripheral blood mononuclear cells from 79 people with HIV-1 (51 women, 28 men) who were virologically suppressed and followed over a median 6 years of ART. We assessed T-cell counts and expression of activation (CD38⁺HLA-DR⁺), cycling (Ki67⁺), exhaustion (TIGIT⁺PD-1⁺), cytotoxicity (CD107a⁺), and regulatory (FoxP3⁺CD25⁺) markers across memory subsets, and we examined associations with sex and HIV reservoir size and activity.

Results: CD4⁺ T-cell counts increased and CD8⁺ T-cell counts declined over time, improving CD4/CD8 ratios. Immune activation and cycling markers decreased in both T-cell compartments. TIGIT/PD-1 expression declined significantly in CD4⁺ memory subsets but not in CD8⁺ T cells, while CD107a expression remained elevated in effector memory CD8⁺ and CD4⁺ T cells. Regulatory CD4⁺ T cells declined over time, and no significant associations were observed between T-cell phenotypes and HIV reservoir measures or between sexes.

Conclusions: Long-term ART promotes partial immune normalization, including reduced activation and reversal of CD4⁺ T-cell exhaustion. However, persistent expression of CD8⁺ T-cell surrogate markers of exhaustion and stable cytotoxic profiles suggest ongoing antigenic stimulation, potentially driven by HIV or chronic coinfections.

Background: Respiratory viral infections in patients with hematologic malignancies or hematopoietic stem cell transplants (HCTs) are associated with increased morbidity and mortality. However, the hospital presentations and courses of these infections remain under-described.

Methods: We performed a multicenter retrospective cohort study of hospitalized patients with hematologic malignancy or HCT at 2 comprehensive cancer centers between January 2019 and June 2023. We included all patients with acute viral respiratory infection (identified based on a constellation of test results and objective physiology), comparing clinical presentations, care processes, and patient outcomes across pathogens; the primary outcome was the composite of hospital death or discharge to hospice.

Results: We evaluated 385 hospitalizations from 346 unique patients, 162 (42%) of which were for SARS-CoV-2 infection. The primary outcome of death or discharge to hospice occurred in 54 (14%) encounters and did not significantly differ across pathogens (P = .4). We observed higher radiographic assessment of lung edema scores in SARS-CoV-2 infection (median 28 [interquartile range 22-32]) compared with other viral infections (5 [2-9], P < .001). Care process differences across pathogens included antibiotic (SARS-CoV-2 98/162 [60%], respiratory syncytial virus [RSV] 17/28 [61%], rhino/enterovirus 59/91 [65%], influenza 22/33 [67%], and others 69/86 [80%], P = .034) and corticosteroid use (≥ 40 mg prednisone equivalents daily: SARS-CoV-2 99/162 [61%], RSV 10/28 [36%], rhino/enterovirus 30/91 [33%], influenza 9/33 [27%], and others 37/86 [43%], P < .001).

Interpretation: Among hospitalized patients with hematologic malignancies or HCTs, acute viral respiratory infections display similar initial physiology and outcomes regardless of pathogen. These findings may have implications for clinical practice.