Clinical Infectious Diseases最新文献

Background: Respiratory syncytial virus (RSV) is a significant health risk for adults aged 18-59 years with chronic medical conditions.

Methods: This ongoing, randomized, double-blind phase 3 trial evaluates safety and immunogenicity of the RSV vaccine, mRNA-1345, in adults aged 18-59 years at increased risk for RSV-associated lower respiratory tract disease (LRTD). Participants received a single 50-µg (licensed dose) or 30-µg dose. Co-primary immunogenicity objectives were to demonstrate noninferiority of day 29 RSV-A/B neutralizing antibody (nAb) geometric mean titers (GMTs) for the 50-μg dose compared with those observed in adults aged ≥60 years from the phase 3 pivotal efficacy trial. The other primary objective was to evaluate safety and tolerability.

Results: A total of 999 participants received mRNA-1345 (50 µg, n = 502; 30 µg, n = 497). Most solicited adverse reactions (ARs) were mild to moderate with a median duration of 2 days. Day 29 nAb GMTs in the 50-µg group met noninferiority criteria: RSV-A GMT ratio (GMR), 1.2 (95% confidence interval [CI], 1.1-1.3); RSV-B GMR, 1.1 (95% CI, 1.0-1.2). Noninferiority was also demonstrated for seroresponse rate differences: RSV-A, 11.8% (95% CI, 7.8-15.5); RSV-B, 10.8% (95% CI, 5.9-15.6). Immune responses were consistent across subgroups and remained above baseline through day 181.

Conclusions: In adults aged 18-59 years at increased risk for RSV-LRTD, a 50-µg dose of mRNA-1345 was well tolerated and elicited RSV-A and RSV-B nAb responses noninferior to those observed in older adults in the pivotal study, supporting inference of efficacy in this population.

Clinical trials registration: NCT06067230.

Baloxavir marboxil is approved for influenza treatment and post-exposure prophylaxis (PEP). There are limited real-world examples of its use in influenza outbreaks. Here, we describe the use of baloxavir marboxil as PEP to halt an influenza outbreak among a college sports team during the 2024-2025 influenza season.

Background: Patients with pulmonary coccidioidomycosis often experience prolonged symptoms lasting from weeks to months. Limited data exist regarding whether fluconazole prevents development of disseminated disease or shortens symptom duration. We describe factors associated with fluconazole receipt and assess its effect on outcomes among patients with pulmonary coccidioidomycosis.

Methods: Using the MerativeTM MarketScan® Commercial Database, we identified immunocompetent patients ages 18-64 with incident pulmonary coccidioidomycosis during 2017-2023 and continuous enrollment in the 180 days before and after diagnosis. We examined demographic and clinical differences between patients treated versus not treated with fluconazole and performed 1:1 greedy nearest neighbor propensity score matching to control for these differences. We performed bivariate analyses on the matched subset to evaluate patient outcomes by fluconazole receipt.

Results: Among 1448 patients with pulmonary coccidioidomycosis, 659 (46%) received fluconazole. Patients who received fluconazole more frequently had pre-diagnosis symptoms (95% vs 72%, P < .001) and antibiotic prescriptions (68% vs 32%, P < .001) than those who did not. Among the propensity score matched subset (n = 696), hospitalization (4% vs 1%, P = .004) and disseminated coccidioidomycosis (3% vs 0%, P = .006) were more frequent among patients who received fluconazole. The median number of days from diagnosis to last visit for chest pain (50.0 vs 46.5), cough (64.0 vs 39.0), fatigue (63.0 vs 65.5), myalgia (98.0 vs 74.0), and joint pain (93.5 vs 107.5) was not significantly different between treatment groups.

Conclusions: Our results support existing guidelines that fluconazole may not be associated with improved outcomes for certain immunocompetent patients with pulmonary coccidioidomycosis.

There has been an unprecedented surge in cases of Congenital Syphilis (CS), the vertical transmission of syphilis from a pregnant individual to their fetus, with over a 10-fold increase over the last 10 years. Infants may present with a wide variety of clinical presentations, with almost every organ system at risk of injury. Further adding to the intricacy of the disease, the majority of infants will be asymptomatic at birth, but due to ongoing inflammation associated with the disease, there may be a myriad of delayed morbid effects that take years to manifest. Diagnosis and management is dependent on a combination of the presence or absence of overt symptoms of the infant, noninvasive serologic examinations of the infant and pregnant individual, certain radiographic images of the fetus in utero or infant postpartum, indirect blood and cerebrospinal fluid markers of the infant, and the timing and adequacy of treatment of the pregnant individual prior to the delivery. This review is meant to help navigate the complexities of the presentation, diagnostic pathways, and treatment decision making processes required for CS.

The concept of immunity debt is a phenomenon resulting from the suppression of endemic pathogens during the COVID-19 pandemic due to non-pharmaceutical interventions. The reduced circulation of various pathogens during the pandemic, particularly respiratory syncytial virus (RSV), altered typical infectious disease dynamics by reducing levels of population immunity usually acquired through exposure to infection. This concept is demonstrated through the post-pandemic resurgence of diseases such as RSV and group A Streptococcus, and highlights the interplay between reduced pathogen exposure and increased susceptibility in populations. The complexities and nonlinear dynamics of seasonal transmission are observed in differences in pathogen resurgence across regions. These issues highlight the importance of comprehensive disease surveillance and public health strategies in mitigating these long-term epidemiological impacts.