Clinical Infectious Diseases最新文献

Background: Longer-term outcome data following second-line antiretroviral therapy initiation in resource-limited settings is limited, especially in regions where genotypic resistance is inaccessible. This analysis evaluated extended efficacy and tolerability data from the D2EFT study.

Methods: D2EFT is a completed, multicenter, phase IIIB/IV, randomized, open-label trial in 14 low- and middle-income countries. People with human immunodeficiency virus (HIV) who had failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens were switched to 1 of ritonavir-boosted darunavir plus 2 nucleoside reverse transcriptase inhibitors (DRV/r + 2NRTIs), ritonavir-boosted darunavir plus dolutegravir (DTG + DRV/r), or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine (DTG + TDF/XTC), with or without pre-switch genotyping. Here we report virological suppression at 96 weeks, defined as HIV RNA <50 copies/mL in a modified intention-to-treat population.

Results: Between November 2017 and January 2022, 1190 participants were screened, 828 were randomized, and 826 were included in the analysis. At week 96, the proportions of participants with HIV RNA <50 copies/mL were 191/251 (76.1%) in DRV/r + 2NRTIs, 215/251 (85.7%) in DTG + DRV/r, and 231/283 (81.6%) in DTG + TDF/XTC. The treatment differences (95% confidence intervals [CIs]) in proportions achieving virological suppression were 9.6% (2.7, 16.4) in DTG + DRV/r and 9.0% (1.4, 16.6) in DTG + TDF/XTC, compared to DRV/r + 2NRTIs. Intermediate or high-level dolutegravir resistance was identified in 3/27 (13%) of virological failures in individuals taking DTG + TDF/XTC but in no one taking DTG + DRV/r. No darunavir resistance was observed.

Conclusions: After 96 weeks of follow-up, DTG + DRV/r and DTG + TDF/XTC demonstrated virological superiority over DRV/r + 2NRTIs after first-line NNRTI-failure. However, emerging dolutegravir resistance, which was observed only in individuals taking DTG + TDF/XTC, requires ongoing global surveillance.

Background: Screening for syphilis increasingly relies on positive treponemal rather than nontreponemal tests (rapid plasma reagin [RPR]). We compared ocular syphilis in patients with nonreactive versus positive RPR.

Methods: We conducted a retrospective observational cohort study of ocular syphilis treated at 2 New England hospitals during 1996-2021 based on ophthalmologist-diagnosed eye findings and positive treponemal serology, regardless of RPR. We excluded patients with alternative diagnoses. We categorized RPR into nonreactive RPR, low-titer RPR (<1:8), and high-titer RPR (≥1:8) and compared early and long-term response to therapy.

Results: Our sample included 115 patients with ocular syphilis (median follow-up, 2.5 years): 25 (22%) with nonreactive RPR, 21 (18%) low-titer RPR, and 69 (60%) high-titer RPR. Compared with nonreactive and low-titer RPR, people with high-titer RPR were younger (mean 47 years, P < .001), more likely to be male (93%, P < .001) and more likely to be diagnosed with human immunodeficiency virus (49%, P < .001). People with nonreactive and low-titer RPR were less likely than those with high-titer RPR to have posterior uveitis/panuveitis (32% and 29% vs 75%, P < .001) or abnormal cerebrospinal fluid (26% and 35% vs 75%, P < .001), and more likely to present with chronic eye findings (20% and 29% vs 1%, P < .001). In long-term follow-up, eye findings improved and did not recur in most patients (62% nonreactive, 68% low-titer, 96% high-titer RPR); improved but recurred in 29%, 11%, and 4%, respectively; and were stable in 10%, 21%, and 0%, respectively.

Conclusions: Patients with ocular syphilis and nonreactive RPR are similar to patients with low-titer RPR, and antibiotic therapy is beneficial in most.

Background: We assessed the impact of pneumococcal conjugate vaccine (PCV) implementation on respiratory syncytial virus-positive, community-acquired alveolar pneumonia (RSV-CAAP) in young children in southern Israel.

Methods: This study was nested within a prospective population-based active surveillance system during 2004-2019. All children <60 months old residing in the region and served by the region's only hospital were included. A negative binomial regression model was used to evaluate the impact of PCV on the incidence of all-cause CAAP and RSV-CAAP and was the basis for estimating averted episodes.

Results: A total of 7640 all-cause CAAP episodes were observed; 50% were tested for RSV, of which 42% were positive. Shortly after PCV13 implementation, all-cause CAAP and RSV-CAAP rates markedly declined, stabilizing within 3-4 years. The mean annual hospitalization rates for all-cause CAAP and RSV-CAAP declined by 47% (95% CI: 40%-53%) and 29% (95% CI: -2% to 51%), respectively, during the late-PCV period, compared with the expected rates. This translated to a reduction in the mean annual incidence of 3.73 cases of all-cause CAAP/1000 children (95% CI: 2.98-4.58) and 0.50 cases of RSV-CAAP per 1000 children (95% CI: -.05 to 1.13). The highest incidences of averted cases occurred in children aged 12-23 months.

Conclusions: The observed dynamics of hospitalizations due to all-cause CAAP and RSV-CAAP following PCV implementation are consistent with the notion of a synergistic role of RSV and pneumococcus in CAAP in young children.

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.