International Journal of Infectious Diseases最新文献

Background: The clinical significance of Candida infection in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains poorly defined.

Methods: This multicenter cohort study analyzed 11,925 hospitalized AECOPD patients from ten centers in China, grouped by Candida infection status. Subgroups were analyzed by Candida species and invasiveness. Primary outcome was 3-year all-cause mortality; secondary outcomes included in-hospital mortality, invasive mechanical ventilation (IMV), non-invasive ventilation (NIV), and intensive care unit (ICU) admission. Propensity score matching and Cox regression were used to adjust for confounders.

Results: Candida-positive AECOPD patients showed significantly worse short-term outcomes, including increased IMV (7.2% vs 3.8%) and NIV use (31.8% vs 18.2%), more ICU admissions (12.7% vs 8.9%), and prolonged hospitalization (15.97 vs 11.16 days, p < 0.001). No significant difference was observed in 30-day mortality between groups (aHR 1.13, 95% CI 0.63-2.03), but 3-year mortality was significantly higher (41.2% vs 30.5%, p < 0.001) in Candida positive group. Subgroup analyses showed no significant differences by species or invasiveness.

Conclusion: Respiratory Candida infection is associated with worse short-term clinical outcomes and increased 3-year mortality in AECOPD patients, but is not an independent risk factor for in-hospital mortality. Neither species nor invasiveness classification offered prognostic value. Screening may identify high-risk patients, but evidence does not support species-specific or β-D-glucan (BDG)-guided therapy among this population.

Background: To determine long-term immunogenicity and reactogenicity of different SARS-CoV-2 mRNA-vaccines in a population ≥75 years in a randomized trial.

Methods: Participants were randomised to receive either BNT162b2 30µg or double booster dose mRNA-1273, i.e.100µg, as 3^rd and 4^th vaccination (1^st and 2^nd booster). Primary endpoint was rate of 2-fold geometric mean titre (GMT) antibody increase 14 days after vaccination targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. Secondary endpoints included neutralising capacity against wild-type and 25 variants at 14 days (D14) and 12 months (M12). Safety was assessed by monitoring adverse events (AEs) for seven days after vaccination.

Findings: Between Nov-2021 and Sep-2022, 322 participants received a SARS-CoV-2 vaccine as a 1^st (Part A) or 2^nd booster (Part B). Primary endpoint results have been published previously. In Part A, it was reached by 100% in both vaccine arms with a higher GMT increase in the mRNA-1273 arm (ratio 1.64). At M12, GMT of anti-RBD IgG was slightly higher than at D14 (9,319.7 vs. 8,568.4IU/mL) in the BNT162b2 arm while in the mRNA-1273 arm, GMT was equal (14,163.8 vs.14,266.7IU/mL at D14.) In Part B, primary endpoint was reached by 78.5% subjects in the BNT162b2 and 87.2% in the mRNA-1273 arm (p=0.056), respectively, with a higher GMT increase of anti-RBD IgG for mRNA-1273 (ratio 1.38). At M12, GMT of anti-RBD IgG was markedly lower than at D14 (9,962 vs. 15,248.2IU/mL) in the BNT162b2 arm as well as in the mRNA-1273 arm (12,024.3 vs. 21,325.6IU/mL). Higher neutralising capacity in individuals boostered with mRNA-1273 was detected against wild-type and 15/25 tested variants. Less participants in mRNA-1273 arm had vaccine-related AEs (29.6% vs. 38.5%), but severity was more frequently grade 2 (n=38, 28.1 % vs. 22, 16.3%).

Interpretation: Long-term serological immunogenicity and virus neutralization capacity in subjects ≥75 years was numerically better with a mRNA-1273 100µg booster with comparable safety profile.

Aim: To identify risk factors associated with poor long-term outcomes in patients with tuberculous pleurisy (TP) through a 9-year prospective cohort study.

Methods: From May 2014 to November 2018, a total of 464 patients diagnosed with TP were enrolled at Beijing Chest Hospital and followed up until November 2023, with a median follow-up duration of 7.1 years. Poor outcomes were defined as the occurrence of secondary empyema, recurrent pulmonary tuberculosis, or recurrent TP. Cox proportional hazards regression models were used to analyze prognostic factors associated with poor outcomes.

Results: Bilateral TP was independently associated with an increased risk of poor outcomes (adjusted hazard ratio [aHR] 2.68, 95% CI 1.41-5.09, P=0.003). Patients receiving extended anti-tuberculosis therapy also exhibited a significantly higher risk (aHR 3.55, 95% CI 2.05-6.15, P < 0.001). In contrast, standardized treatment was associated with a 93% reduction in the risk of poor outcomes compared with non-standardized treatment (aHR 0.07, 95% CI 0.02-0.24, P < 0.001).

Conclusion: Long-term prognosis in patients with TP is influenced by both disease severity, as reflected by bilateral pleural involvement and the need for extended treatment regimens, and the quality of clinical management, particularly adherence to standardized therapy. Early diagnosis and strict implementation of guideline-recommended treatment should be prioritized, especially among patients at higher risk of adverse outcomes.

Background: Tropheryma whipplei (T. whipplei) is the causative bacterium of Whipple's disease (WD), a chronic and systemic infectious condition that predominantly affects the gastrointestinal tract. Sporadic cases of T. whipplei pneumonia have been documented recently.

Methods: This multicenter retrospective observational study was conducted on patients with T.whipplei positive respiratory specimens admitted to Peking University People's Hospital and China-Japan Friendship Hospital, from Apr 2021 to Jul 2024. Metagenomic next-Generation sequencing (mNGS) was performed using the patient'sbronchoalveolar lavage fluid (BALF), and the quantitative polymerase chain reaction (qPCR) of T. whipplei was also adopted. The clinical data of patients were systematically evaluated.

Results: Among 91 patients (aged 25-82, mean 57; 48% male), common symptoms included cough (60%), expectoration (48%), dyspnea (42%), and fever (30%). Notably, 22% were asymptomatic. Besides,20 patients (22%) had a pre-existing condition of interstitial lung disease. Among all 91 patients, 14 were diagnosed with pneumonia, while the remaining 77had bacterial colonization.Pneumonia cases showed higher T. whipplei mNGS reads than colonization (P=0.0298). Samples testing positive for T. whipplei by qPCR exhibited significantly higher mNGS sequence reads compared to qPCR-negative samples (P<0.0001). All pneumonia patients received antibioticstherapy tailored to their condition. One died from respiratory failure, while the remaining 13 recovered.

Conclusion: The application of mNGS on respiratory specimens stands as an exceptional diagnostic modality, proficient in identifying rare microbial infections, exemplified by those induced by T. whipplei. Future research should launch prospective trials to optimize regimens, assess outcomes, and track long - term survival precisely.

Objective: To evaluate the effectiveness of viral load (VL)-based triage strategies for human papillomavirus (HPV)-positive women, utilizing data from two large cohort screening studies.

Methods: We analyzed 1,656 HPV-positive cases identified among 25,419 screening participants. Collected data included HPV testing, cytology, and pathologically confirmed diagnoses. VL-based triage strategies were compared to a guideline-recommended cytology-based triage. The cycle threshold (Ct) value, representing HPV VL, was used for triage, with the 75th percentile of Ct values established as the cut-off. Outcomes were assessed for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+.

Results: The mean participant age was 43 ± 7.99 years. Two triage strategies were compared: (1) HPV-16/18 & other types with Ct ≤ the 75th percentile cut-off (higher viral load), and (2) HPV-16/18 & other types with cytology (referring those with ≥ atypical squamous cells of undetermined significance [ASCUS] for colposcopy). The VL-based strategy demonstrated higher sensitivity than the cytology-based strategy for detecting CIN2+ (91.52% vs. 85.27%, p = 0.016) and was comparable for detecting CIN3+ (95.60% vs. 96.70%, p = 1.000). Similarly, the strategy using HPV-16/18 with Ct ≤ 75th & other types with Ct ≤75th was also comparable to the cytology-based approach for detecting both CIN2+ (87.05% vs. 85.27%, p = 0.636) and CIN3+ (95.60% vs. 96.70%, p = 1.000).

Conclusion: Viral load-based triage effectively identifies cervical precancer/ cancer in HPV-positive individuals without cytology, allows single-sample collection, reduces multiple visits, and may be most useful where cytology is unavailable or unreliable-acknowledging an increased colposcopy referral.

Introduction: In Sri Lanka, reliable diagnostics for rickettsial infections are limited. We assessed the burden, seroprevalence, and molecular diversity of rickettsial infections in hospitalized patients with acute undifferentiated febrile illness(AUFI).

Methods: AUFI patients were enrolled from the Western (n=540) and Central (n=260) Provinces. Clinical and exposure data, acute and convalescent sera, and buffy coat/eschar samples were collected. Orientia tsutsugamushi(OT) and Rickettsia spp. were detected using OT-specific (47 kDa) and pan-Rickettsia (17 kDa) qPCR assays. Group-specific IgG ELISAs were performed for scrub typhus(STG), typhus group(TG), and spotted fever group(SFG). Acute infection was defined by qPCR positivity and/or a ≥4-fold rise in IgG titres. Genetic diversity was assessed using OT 56kDa TSA and Rickettsia ompB gene sequencing.

Results: qPCR identified 38/800(5%) STG and 25/800(3%) TG/SFG infections. Among participants with paired sera (n=493), acute infections included 25(5%) STG, 11(2%) TG, and 17(3%) SFG cases. Overall, rickettsioses accounted for 86/800(11%) of AUFI cases. SFG seroprevalence was higher in the Central Province (17% vs 6%), while STG seroprevalence was higher in the Western Province (20% vs 13%). Genetic analysis on OT cases showed clustering with Karp, Kato, Buie, TH1811, TH1826 and Ikeda strains. Two cases of rickettsial infections were speciated as R. felis and R. sibirica. Only 19% of acute cases were clinically recognized and 58% received doxycycline.

Conclusion: Rickettsioses were under-recognized, highlighting the need for combining qPCR and ELISA diagnostics to strengthen clinical management and surveillance.

Background: The global SARS-CoV-2 pandemic highlighted the urgent demand for reliable serological assays to track infection and immune responses. Enzyme immunoassays (EIA) targeting viral antibodies provide a practical platform for quantifying antibody responses in humans and animals, serving as a framework for future pandemic preparedness and response.

Objectives: This study aimed to develop and evaluate an in-house EIA for the detection of total antibodies against SARS-CoV-2 using recombinant antigens: Spike Protein (SP), Receptor Binding Domain (RBD), and Nucleocapsid Protein (NP).

Methods: Recombinant antigens were conjugated to horseradish peroxidase (HRP) for detection in a double-sandwich ELISA format. The optimized assay was compared with an electrochemiluminescence assay (ECLIA) to determine cut-off values via receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden's J statistic were calculated. Assay optimization included testing dilutional linearity, incubation time, and reaction volume. The assay was applied to human and animal serum samples to assess versatility.

Results: Among the antigens tested, the receptor binding domain (RBD) exhibited the highest signal intensity and demonstrated dilutional linearity, outperforming both the spike protein and nucleoprotein in assay sensitivity. The assay demonstrated a sensitivity of 85% and specificity of 100%, with a PPV of 100% and an NPV of 68%. The high Youden's J statistic (0.85) and clear separation between true positive and negative samples underscore the robustness of the RBD antigen in reliably detecting SARS-CoV-2-specific antibodies for serological diagnostics. The optimized EIA protocol allowed for a reduced incubation time without compromising assay performance, and increasing the reaction volume two-fold did not result in a significant gain in signal intensity.

Conclusions: The RBD-based EIA provides a reliable, efficient platform for COVID-19 serological surveillance, suitable for both human and animal testing, and supports broader applications in vaccine evaluation and One Health monitoring.

Background: Sepsis-induced myocardial injury (SIMI) is a severe complication with high mortality. Beta-blocker therapy in SIMI remains controversial, lacking large-sample evidence.

Objective: To evaluate beta-blocker impact on mortality in SIMI patients using MIMIC-IV and eICU databases.

Methods: A retrospective cohort study based on MIMIC-IV (2008-2022) and eICU (2014-2015) databases included adult SIMI patients meeting Sepsis-3.0 criteria with elevated cardiac troponin. The primary exposure was beta-blocker use during ICU stay, and the primary outcome was in-hospital all-cause mortality. 1:1 propensity score matching was used to balance baseline characteristics, with multiple sensitivity analyses to verify result robustness.

Results: MIMIC-IV included 2,368 SIMI patients (1,338 using beta-blockers); eICU included 3,805 patients (1,030 using beta-blockers). After propensity score matching (MIMIC-IV: 837/group; eICU: 902/group), beta-blocker use was associated with a significant reduction in in-hospital mortality (MIMIC-IV: 19.7% vs 29.9%, OR=0.75, 95%CI: 0.60-0.94; eICU: 28.6% vs 35.1%, OR=0.70, 95%CI: 0.56-0.88). Long-term mortality was lower by 39% (28-day), 33% (90-day), and 27% (1-year) (all P<0.001). Multiple sensitivity analyses confirmed robustness (E-value: 2.00-2.21). Severely ill patients (SOFA≥8) had the greatest mortality reduction associated with beta-blocker use (55%). Prolonged hospital stay was consistent with a survival benefit rather than adverse effects.

Conclusions: Beta-blocker use is associated with reduced mortality and better long-term survival in SIMI patients, requiring prospective validation.

Objective: We explored factors contributing to the low human MERS-CoV prevalence in Africa by assessing MERS-CoV epidemiological and genomic features.

Methods: We followed the PRISMA guidelines. We searched for articles on epidemiological and virological MERS-CoV characteristics in humans and camels in Africa until August 2025. We used a generalised linear mixed-effects model to calculate pooled proportions. We identified relevant polymorphisms in African MERS-CoV lineages compared with the prototypic EMC/2012 and contemporary Arabian MERS-CoV (clade B5).

Results: We included 53 articles, with 31 used in the meta-analysis. Kenya, Egypt, and Ethiopia contributed to 66.03% of all included studies. Pooled MERS-CoV RNA positivity in African dromedaries was 6.09%, with juveniles (15.29%) having a higher incidence than adults (4.51%). The pooled MERS-CoV seroprevalence was 73.67%, with adults (80.96%) higher than juveniles (36.02%). In human-focused studies, only nine PCR-confirmed MERS cases were reported, six travel-associated and three autochthonous cases, despite a pooled seroprevalence of 2.4%. Genomic analyses identified MERS-CoV clade C-specific polymorphisms in the Spike and accessory genes with putative phenotypic impact.

Conclusion: We found the highest MERS-CoV RNA positivity in young dromedaries. Elevated MERS-CoV seroprevalence in mainly asymptomatic camel-exposed humans suggests an underestimation of MERS-CoV infections in Africa. The ongoing MERS-CoV evolution emphasises the need for active genomic surveillance to monitor signatures of human adaptation.