Open Forum Infectious Diseases最新文献

Background: Dengue virus (DENV) is an arboviral pathogen found in >100 countries and a source of significant morbidity and mortality. While the mechanisms underpinning the pathophysiology of severe Dengue are incompletely understood, it has been hypothesized that antibodies directed against the DENV envelope (E) protein can facilitate antibody-dependent enhancement (ADE) of the infection, increasing the number of infected cells and the severity of disease in an exposed individual. Accordingly, there is interest in defining mechanisms for directly targeting DENV-infected cells for immunologic clearance, an approach that bypasses the risk of ADE.

Methods: We have previously demonstrated that antibodies specific to DENV nonstructural protein 1 (NS1) can opsonize and facilitate the phagocytic clearance of DENV-infected cells. However, it is currently unclear if other DENV antigens are expressed on the surface of infected cells and if these antigens can be targeted by antibody-dependent clearance mechanisms.

Results: In this study, we demonstrate that DENV structural proteins are expressed on the surface of DENV-infected cells and that these antigens can be opsonized by both DENV-immune sera and monoclonal antibodies. In addition, DENV E-specific antibodies can facilitate phagocytic uptake of material from DENV-infected cells, resulting in the target-cell membrane localizing to endosomes of the engulfing phagocyte. Notably, there was no selective enrichment of DENV genomic material in monocytes that had phagocytosed DENV-infected cell material compared with nonphagocytic monocytes.

Discussion: In their totality, these data reinforce the concept that DENV E-reactive antibodies have a multifaceted role in DENV immunity and pathogenesis beyond neutralization and/or infection enhancement.

[This corrects the article DOI: 10.1093/ofid/ofae498.].

A post hoc analysis of maternally derived antibodies at birth and age 2 months following second trimester maternal Tdap vaccination between 20 and 24 weeks' gestational age (GA) showed a faster decay rate of Tdap-related immunoglobulin G in early preterms born before 32 weeks' GA compared with moderate-to-late preterms and full-terms. This is different from previous studies and merits further research.

Background: For clinicians treating patients with infective endocarditis (IE), identifying the causative microorganisms poses a critical diagnostic challenge. Standard techniques including blood and heart valve cultures often yield inconclusive results. According to the recent 2023 Duke-ISCVID Criteria, molecular methods represent potent tools to enhance this aspect of IE diagnostics and guide subsequent therapeutic strategies.

Methods: We retrospectively analyzed data from 124 consecutive patients who underwent heart valve surgery due to suspected IE at München Klinik Bogenhausen. The standard diagnostic pathway, which included blood culture, valve culture, histopathological analysis, and polymerase chain reaction (PCR)/sequencing, was compared with the enhanced diagnostic pathway, which included fluorescence in situ hybridization + PCR/sequencing (FISHseq) instead of PCR/sequencing alone. The aim of this study was to assess the added value of combining standard diagnostics with molecular methods such as PCR/sequencing or FISHseq for the diagnosis of IE and the potential impact on therapy.

Results: Standard diagnostic methods and PCR/sequencing yielded inconclusive results in 57/124 cases (46.0%). FISHseq provided an added value for diagnostics in 79/124 cases (63.7%) and potentially would have impacted therapy in 95/124 (76.6%) of cases. By adding data through direct visualization and characterization of microorganisms, FISHseq reduced the number of inconclusive cases by 86.0%.

Conclusions: The comparison of 2 molecular diagnostic tools for IE from the same heart valve emphasizes the value of molecular methods including molecular imaging by FISH for IE diagnostics and supports the 2023 Duke-ISCVID Criteria.

Background: There is limited evidence on point-of-care ultrasound for tuberculosis (TB), but studies suggest high sensitivity, especially for lung ultrasound (LUS). However, insufficient data are available on specificity of the examination and its generalizability to a broader patient population.

Aims: Our study aimed to establish accuracy for lung, chest, and abdominal ultrasound, individually and in combination, for TB diagnosis.

Methods: We conducted a prospective diagnostic accuracy study among consecutive adult out- and inpatients with probable TB in three German referral hospitals. We applied a comprehensive standardized ultrasound protocol. TB diagnosis was established by a microbiological reference standard including polymerase chain reaction and culture.

Results: A total of 102 participants originating from 30 different countries were enrolled. HIV prevalence was 7/99 (7%) and 73/102 (72%) had confirmed TB. TB was limited to the lungs in 15/34 (44%) of refugees and 27/39 (69%) in nonrefugees. Focused assessment with sonography for HIV-associated tuberculosis had a sensitivity of 40% (95% confidence interval [CI], 30-52) and specificity of 55% (95% CI, 38-72). Additional findings, such as small subpleural consolidations on LUS had a high sensitivity (88%; 95% CI, 78-93), but a low specificity (17%; 95% CI, 8-35). Larger consolidations in the lung apices had a sensitivity of 19% (95% CI, 12-30) and a specificity of 97% (95% CI, 83-100).

Conclusions: Our study establishes the first data on LUS performance against a comprehensive reference standard. Overall, our data suggest that ultrasound does not meet the requirements for triage but previously described and novel ultrasound targets in combination could aid in the clinical decision making.Registry: DRKS00026636.

Background: The recognition of autoimmune causes of encephalitis has led to epidemiological shifts in the worldwide characteristics of encephalitis. N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis leads to well-established complex neuropsychiatric manifestations. In low- and middle-income countries, including Vietnam, its relative incidence, especially in children, is unknown and most neurologists currently consider infectious encephalitis prior to autoimmune etiologies.

Methods: The study was prospectively conducted at Children's Hospital 1 in Ho Chi Minh City between March 2020 and December 2022. Any child admitted to the Department of Infectious Diseases and Neurology fulfilling the case definition of encephalitis was eligible to participate. Cerebrospinal fluid samples were collected alongside meta-clinical data for analysis.

Results: We recruited 164 children with a clinical diagnosis of encephalitis. Etiologies were determined as NMDAR antibody encephalitis in 23 of 164 cases (14.0%), Japanese encephalitis virus in 14 of 164 (8.5%), and herpes simplex virus in 4 of 164 (2.4%). Clinical categorizations suggested idiopathic viral encephalitis in another 71 (43.3%), and autoimmune encephalitis of unknown origin in the remaining 52. Factors including demographics, specific clinical features, cerebrospinal fluid and electroencephalogram findings, and length of hospital stay were significantly different between NMDAR antibody encephalitis and Japanese encephalitis.

Conclusions: At a tertiary children's hospital in Vietnam, the prevalence of NMDAR antibody encephalitis exceeds that of Japanese encephalitis, the most common infectious encephalitis cause in Southeast Asia. NMDAR antibody encephalitis is associated with long hospital stay and poor outcomes. These findings should change pediatric diagnostics, to earlier consider autoimmune treatments in this clinical setting.

Histoplasma capsulatum is a pathogenic dimorphic fungus with evolving epidemiology. Initially described as endemic to the Ohio and Mississippi river valleys, the infection now regularly occurs in central and eastern United States, with cases reported across the entire country. Transmission happens via inhalation of conidia during activities that disturb fungal hyphae. Sporadic cases related to individual exposures now outnumber work-related outbreak cases in the United States. We describe 2 fatal cases of histoplasmosis in Rochester, New York, associated with exposure to bat guano as a fertilizer for cannabis cultivation, including 1 case in which it was commercially obtained.

Respiratory viral infection may increase infection with Burkholderia pseudomallei progressing to clinical disease (melioidosis). This data linkage study evaluated associations between melioidosis and SARS-CoV-2 or influenza. Among 160 melioidosis cases, there was no difference in risk factors, vaccine status, or disease severity between 17 with viral co-infection and 143 without.

Background: The prophylactic use of quinolones in the setting of allogeneic hematopoietic stem cell transplantation (allo-HCT) is controversial and solid evidence is missing, particularly in children.

Methods: In this single-center retrospective study, we compared outcomes in patients receiving (n = 74) or not receiving (n = 70) levofloxacin (LVX) prophylaxis, assessing overall survival, event-free survival, acute graft-versus-host disease (aGvHD) and bloodstream infection incidence, and infection-related mortality. Gut microbiota composition was analyzed in a subgroup using 16S rRNA sequencing of stool samples collected pre-HCT and at engraftment.

Results: We analyzed 144 allo-HCT in 143 patients performed for any indication. No differences were found in the 2 groups regarding main HCT outcomes, namely, cumulative incidence of aGvHD (37.9% vs 43.5%; P = .733), grade III-IV aGvHD (12.2% vs 8.7%; P = .469), gut aGVHD (12.2% vs 17.5%; P = .451), bloodstream infections (25.6% vs 34.1%; P = .236) and death from bacterial infection (9.5% vs 4.3%; P = 0.179). In patients experiencing bacterial infections, those receiving prophylaxis showed higher incidence of quinolone-resistant strains (P = .001). On a subgroup of 50 patients, we analyzed the gut microbiota composition, showing a lower abundance of Blautia (P = .015), Enterococcus (P = .011), and Actinomyces (P = .07) at neutrophil engraftment in patients receiving LVX prophylaxis.

Conclusions: LVX prophylaxis in the setting of allo-HCT does not prevent infective complications and increases the prevalence of antibiotic-resistant strains.

Background: To investigate the prevalence of concomitant bacterial infection across common viral infections.

Methods: This population-based cohort study included patients infected with influenza A and B (FLUA, FLUB) and respiratory syncytial virus (RSV) in Ontario between 2017 and 2019 and patients with SARS-CoV-2 between 2020 and 2021. Specific bacteria present in concomitant infections were identified. Concomitant infections were further classified into different categories (eg, coinfection -2 to +2 days from viral infection and secondary infection >2 days after viral infection). We used logistic regression models to estimate the odds of bacterial infections for FLUA, FLUB, and RSV relative to SARS-CoV-2 while adjusting for confounders.

Results: A total of 4230 (0.5%, 885 004) viral cases had concomitant bacterial infections, encompassing 422 of FLUB (4.7%, 8891), 861 of FLUA (3.9%, 22 313), 428 of RSV (3.4%, 12 774), and 2519 of COVID-19 (0.3%, 841 026). The most prevalent species causing concomitant bacterial infection were Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa. When compared with SARS-CoV-2, the adjusted odds ratio for bacterial infection was 1.69 (95% CI, 1.48-1.93) for FLUA, 2.30 (95% CI, 1.97-2.69) for FLUB, and 1.56 (95% CI, 1.33-1.82) for RSV. The adjusted odds of coinfection in patients with SARS-CoV-2 were lower but higher for secondary infection as compared with the other viruses.

Conclusions: A higher prevalence and risk of concomitant bacterial infection were found in FLUA, FLUB, and RSV as compared with SARS-CoV-2, although this is largely driven by coinfections. Ongoing surveillance efforts are needed to compare the risk of concomitant infections during periods when these viruses are cocirculating.