Open Forum Infectious Diseases最新文献

Highly pathogenic avian influenza A (H5) virus continues to spread in animals with ongoing concern for potential human transmission. We describe an adaptable H5 screening approach that integrates clinical laboratory workflows with research-developed assays. This strategy efficiently screened thousands of samples, providing a practical and scalable model for H5 surveillance.

Infectious diseases physicians serve on the frontline of disease prevention, outbreak mitigation, and direct patient care across the healthcare continuum. To reverse troubling trends in the ID workforce, policymakers, healthcare administrators, and the public must understand the essential societal role of ID physicians. Solutions include adopting new compensation models, loan forgiveness for medical specialties where demand exceeds supply, reformed immigration policies for staffing medically underserved areas and reinvestment in public health. A receding ID workforce will result in delayed ID specialty care, worse clinical outcomes, worsening antibiotic resistance, increased healthcare costs, decreased pandemic preparedness, and an overall sicker nation.

Background: Babesiosis, caused by the parasitic blood-borne piroplasm Babesia microti, is emerging in the Northern hemisphere. We aimed to study long-term symptoms of patients with B microti infection in New York.

Methods: A prospective longitudinal cohort study of human babesiosis was conducted at Stony Brook University Hospital. Inclusion criteria were age ≥18 years with positive blood smear for Babesia spp. Symptoms were assessed in patients at presentation and at 1, 6, and 12 months by 3 validated surveys: a visual analog scale, a quality of life (QOL) questionnaire, and the 36-Item Short Form Survey (SF-36).

Results: In total, 38 patients with acute B microti infection (26% female; age range, 54-73 years) were enrolled from 2020 to 2022. Compared with baseline, the visual analog scale total symptom scores (with high scores representing worse status) significantly decreased at 6-month follow-up for the immunocompetent (n = 9; P < .001) and immunocompromised groups (n = 6; P < .001). Scores remained significantly higher in the immunocompromised group (ratio, 2.6; P = .045). At 1-year follow-up, the scores in the 2 groups tended to be similar (ratio, 0.9; P = .82). Within QOL concept scores (with low scores representing worse status), physical functioning significantly increased after 6 months of follow-up in both cohorts (immunocompetent, n = 10 [P = .004]; immunocompromised, n = 5 [P = .008]) but was still significantly lower in the immunocompromised group at that time (ratio, 0.7; P < .001). By the 12-month follow-up, physical functioning scores in the 2 groups appeared to converge, though the difference remained borderline significant (ratio, 0.9; P = .06).

Conclusions: The time to convalescence was similar among patients with babesiosis, though immunocompromised patients tended to have more prolonged symptoms and worsened QOL after babesiosis at 1-year follow-up, compared with immunocompetent patients.

Background: Respiratory syncytial virus (RSV) and influenza virus are leading causes of respiratory infections, causing substantial numbers of hospitalizations and deaths, particularly among vulnerable groups such as infants and older adults. While the burden of influenza virus infection is well-documented, the burden of RSV infection in the adult population is often underestimated due to diagnostic challenges and infrequent standard-of-care testing. This study aimed to estimate the incidence of general practitioner (GP) visits, hospitalizations, and deaths attributable to RSV and influenza virus infections in French adults aged ≥50 years, with a focus on ≥65 years, using a time-series model-based approach. In addition, costs associated with hospitalizations were calculated.

Methods: Cyclic Poisson regression models and weekly data from French medical administrative databases and electronic medical records over ten epidemic seasons (2010-2020) were used to estimate incidences for RSV and influenza. The results were stratified by age group, diagnosis causes (respiratory and cardiorespiratory) and diagnosis type (primary and secondary). Average costs per hospitalization were calculated and multiplied by the number of hospitalizations estimated.

Results: Among adults aged ≥65 years, we estimated RSV infection was responsible for 647 619 GP visits 24 319 hospitalizations, and 878 deaths per year. Incidence rates for GP visits for RSV were twice as large as for influenza; hospitalization rates were similar and mortality was lower. The mean annual cost of RSV-attributable hospitalizations was 105 million €, similar to influenza.

Conclusions: This study highlighted the burden of RSV disease in the adult population in France is higher than previous reported. We envisage that this model-based approach will be instrumental in evaluating the impact of RSV vaccination campaigns.

Aim: To assess the ability of Giannella Risk Score (GRS), Increment Score (IS), and modified-Increment Score (m-IS) to predict the risk of infection after colonization by OXA-48 producing Enterobacterales (OXA-48-Ent) and mortality after infection.

Methods: A retrospective cohort study (2020-2022) including 273 patients colonized with OXA-48-Ent. univariable and multivariable analysis to identify predictors for OXA-48-Ent infection at 30 days after colonization and 30-day mortality among infection episodes, including GRS, IS, and m-IS, were performed.

Results: Fifty-seven (20.1%) patients developed an infection during the first year after colonization, with 51 (90%) of 66 infection episodes occurring within the first 30 days. Seventeen (7.8%) of 219 patients with a GRS < 7 developed an infection whereas this occurred in 34 (63%) of 54 with a GRS ≥ 7 (P < .01). GRS was the only independent risk factor for infection at 30 days [aOR = 1.41; (95% CI: 1.26-1.58), P < .01]. 30-day mortality of OXA-48-Ent infection episodes was 27%. Two (7.7%) of 26 infected patients with a modified IS < 8 died whereas this occurred in 15 (40.5%) of 41 with an IS ≥ 8 (P < .01). Independent risk factors for 30-day mortality after infection was IS [aOR = 1.32 (95% CI: 1.10-1.58), P = .01].

Conclusions: A significant proportion of patients colonized by OXA-48-Ent develop infection by its colonizing strain within the first 30 days after colonization. The application of GRS, IS, and m-IS identified OXA-48-Ent colonized patients with a low risk for infection and with low risk of mortality in the case of a confirmed OXA-48-Ent infection.

Background: Zika virus (ZIKV) emergence in 2015-2016 was characterized by high attack rates and a wave of Congenital Zika Syndrome cases that affected several countries in the Americas. The sudden drop in virus transmission in the following years and the lack of a reliable correlate of protection have hampered the development of vaccines. ZIKV neutralizing antibodies (nAbs) responses to natural ZIKV infection provide insights into the potential efficacy of vaccine candidates.

Methods: In this study, we compared anti-ZIKV nAb responses generated by a ZIKV vaccine (TAK-426), to those elicited by natural ZIKV infection in participants from diverse geographic areas using the same neutralizing antibody assay.

Results: Those with a ZIKV infection (inapparent or symptomatic) exhibited higher levels of ZIKV nAbs, than TAK-426 vaccine recipients at all time points. The differences were less pronounced 1 month after TAK-426 dose 2. ZIKV nAb titers in vaccinated recipients were above the calculated threshold of protection at 1 month post-dose 2 for flavivirus (FV)-naive participants and at 1 and 6 months post-dose 2 for FV-primed participants. The kinetics of ZIKV nAbs were similar for both the natural infection and vaccination groups, exhibiting a peak, decline, and stabilization pattern; however, vaccine non-inferiority was not demonstrated.

Conclusions: Our findings suggest that nAbs evoked by the current phase 1 formulation and dosage of TAK-426 may not protect against a ZIKV infection in endemic countries and that a booster dose should be further evaluated.

Among 852 samples sent for QuantiFERON^®-TB Gold Plus Assay (QFN) analysis, between 6% and 11% had IFNγ binding activity, but only 1.2% of indeterminate samples had IFNγ blocking activity. No TB negative samples had blocking activity to IFNγ. Indeterminate QFN results may indicate the presence of blocking anti-IFNγ autoantibodies.

Rural and critical access hospitals serve 15% of the United States population and utilize antibiotics at similar rates and spectrum as larger urban hospitals, making them a priority for antimicrobial stewardship. However, barriers such as insufficient personnel, limited electronic health record capabilities, and financial constraints limit stewardship initiatives. Telestewardship partnerships with urban hospitals offer a promising solution; however, a structured process to develop and implement such programs is not established. This perspective focuses on unmet needs in rural hospitals to provide future direction for improved patient care in these settings. In 2024, UW Health engaged leaders of small and rural hospitals to design a telestewardship program that meets regulatory requirements (ie, Joint Commission Standards). Despite these requested services, financial barriers hindered implementation of telestewardship partnerships. This work underscores the opportunities and challenges faced by rural hospitals and the ongoing need for state and national funding to support these communities.

Background: Bloodstream infections (BSIs) caused by carbapenemase-producing Enterobacterales (CPE) are associated with increased mortality rates. However, limited data exist in Latin America, particularly in regions where bla _NDM is predominant.

Methods: We conducted a retrospective cohort study of adult inpatients with Escherichia coli or Klebsiella pneumoniae BSI at a Peruvian referral hospital between 2020 and 2023. Patients were classified as CPE or non-CPE based on molecular testing. The outcome was 30-day all-cause mortality. Multivariable Cox regression was used to identify independent predictors of mortality, adjusting for confounders selected via a directed acyclic graph.

Results: Among 506 patients, 97 (19.2%) had CPE BSIs, predominantly bla _NDM (63.9%) and bla _KPC (36.1%). Overall, the 30-day mortality rate was 27.3%, significantly higher in the CPE group (52.6% vs 21.3%; P < .001). In multivariable analysis, CPE infection remained independently associated with increased mortality (adjusted hazard ratio [aHR] 1.88; 95% CI 1.19-2.96). Other predictors included age ≥60 years (aHR 1.53), septic shock (aHR 2.93), pneumonia (aHR 1.70), and immunosuppression (aHR 1.72). Among CPE subtypes, Klebsiella pneumoniae Carbapenemase (KPC)-producers conferred the highest mortality risk (aHR 2.64). Concordant empirical antibiotic therapy was not significantly protective after adjustment.

Conclusions: CPE BSIs were independently associated with increased 30-day mortality, with KPC-producing K pneumoniae posing the greatest risk. Despite the predominance of New Delhi Metallo-β-Lactamase (NDM) in our setting, these findings emphasize the clinical severity associated with different carbapenemase types, and the need to tailor interventions accordingly. Strengthening molecular surveillance and ensuring timely access to effective therapies remain critical priorities in NDM-endemic regions, such as Peru.

Background: Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses are widely circulating in North America with unprecedented transmission into novel host species. A high incidence of neurologic disease is observed in carnivores infected with clade 2.3.4.4b HPAI H5N1 viruses, and historical outbreaks of HPAI H5N1 in humans are also associated with neurologic complications, raising concerns about neurotropism and neurovirulence of clade 2.3.4.4b HPAI H5N1 viruses.

Methods: We analyzed virus replication kinetics, cellular tropism, and host responses to infection in human cerebral organoids (hCOs) inoculated with clade 2.3.4.4b HPAI H5N1 viruses compared to a historical clade 1 HPAI H5N1 virus and a 2007 seasonal influenza A virus.

Results: HPAI H5N1 viruses replicated to high titers in hCOs, but replication of the seasonal influenza A virus was not detected. Viral antigen and RNA were detected primarily in neuron- and astrocyte-like cells. Interferon responses to infection with HPAI H5N1 viruses were observed in a small population of bystander cells. Higher levels of cell death and proinflammatory cytokines and chemokines were observed in organoids inoculated with the historical HPAI H5N1 isolate.

Conclusions: Clade 2.3.4.4b HPAI H5N1 viruses exhibit similar neurotropism compared to a historical clade 1 HPAI H5N1 virus. Lower levels of cell death and inflammatory cytokine production induced by clade 2.3.4.4b viruses may indicate reduced neuropathogenic potential of these viruses in humans.