Journal of Infectious Diseases最新文献

Introduction: Effective immune protection against SARS-CoV-2 infection and severe COVID-19 disease continues to change due to viral evolution and waning immunity. We estimated population-level immunity to SARS-CoV-2 for each of the fifty United States (U.S.) and the District of Columbia from January 2020 through December 2023.

Methods: We updated a model of SARS-CoV-2 infections to align with the latest evidence on SARS-CoV-2 natural history and waning of immunity, and to integrate various data sources available throughout the pandemic. We used this model to produce population estimates of effective protection against SARS-CoV-2 infection and severe COVID-19 disease.

Results: On December 30, 2023, 98.6% of the U.S. population had experienced immunological exposure to SARS-CoV-2 through infection and/or vaccination, with 88.3% (95% credible interval (CrI): 78.4%, 95.5%) having had at least one SARS-CoV-2 infection. Despite this high exposure, the average population-level protection against infection was 31.6% (25.1%, 41.2%). Population-level protection against severe disease was 66.1% (59.2%, 74.3%).

Discussion: A new wave of SARS-CoV-2 infections and COVID-19-associated hospitalizations began near the end of 2023, with the introduction of the JN.1 variant. This upturn suggests that the U.S. population remains at risk of SARS-CoV-2 infection and severe COVID-19 disease despite the high level of cumulative exposure in the United States. This decline in effective protection is likely due to both waning and continued viral evolution.

Background: Various underlying medical conditions (UMCs) elevate the risk of influenza-associated hospitalization. We evaluated how these rates changed by type and number of UMCs.

Methods: Retrospective cohorts were constructed among adult members of 2 health systems aged ≥18 years with prior healthcare utilization. Across the 2016-2017 to 2019-2020 seasons, we estimated influenza-associated hospitalization rates by type and number of UMCs. Hospitalizations were defined using discharge diagnoses or laboratory confirmation. We calculated adjusted rate ratios (aRRs) using Poisson regression controlling for site, season, and demographic characteristics. We used causal mediation to estimate the effect of UMCs on influenza-associated hospitalization accounting for influenza vaccination status.

Results: Among 870 888 cohort members, 1403 were hospitalized with influenza at least once within a season across 4 seasons. The aRR for influenza-associated hospitalization was highest for individuals with congestive heart failure (4.2 [95% confidence interval, 3.6-4.9] compared to those without congestive heart failure). The aRRs also increased with each additional UMC compared to those with no UMCs. The effect of UMCs on influenza-associated hospitalizations was higher when not mediated by vaccination status; for those with ≥4 UMCs compared to no UMCs, rates were about 60% higher.

Conclusions: The burden of baseline medical conditions is associated with higher rates of influenza-associated hospitalization. Among those with varying types and number of UMCs, if vaccination prevalence had been lower than observed, influenza-associated hospitalization rates would have been higher. These findings highlight the importance of preventive medical care and annual influenza vaccination in reducing influenza-associated hospitalizations, particularly for individuals at high risk.

Background: The CYP2D6 enzyme plays a critical role in the metabolism of primaquine, the most widely used drug for the radical cure of Plasmodium vivax malaria. Impaired CYP2D6 activity has been associated with an increased risk of relapse. However, the overall impact of CYP2D6 on infection dynamics is still not fully understood. We hypothesized that individuals with impaired CYP2D6 activity develop partial immunity more rapidly due to the ineffective clearance of hypnozoites.

Methods: To test this hypothesis, we conducted a community-based study involving ∼1300 individuals genotyped for CYP2D6 and assessed repeatedly for P. vivax using molecular diagnosis. This approach allowed us to detect and monitor submicroscopic and asymptomatic infections over a 4-year follow-up period.

Results: In our cohort, children with impaired CYP2D6 activity exhibited a higher frequency of P. vivax infections compared with those with normal enzyme activity. This pattern changed during the second decade of life, as the prevalence of P. vivax infection increased in adolescents with normal enzyme activity (P = .0008, Generalized additive mixed model). Consistent with this, parasite densities were lower in adults with impaired CYP2D6 activity compared with younger individuals with normal enzyme activity (P = .0383, Linear mixed model).

Conclusions: These findings underscore the potential role of CYP2D6 in shaping infection dynamics and malaria immunity in endemic areas.

Asymptomatic influenza virus infection occurs but may vary by factors such as age, vaccination status, or season. We examined the frequency of influenza virus infection and symptoms using data from 2 case-ascertained household transmission studies (2017-2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that met our inclusion criteria, 8% were asymptomatic, 6% had nonrespiratory symptoms, 23% had acute respiratory symptoms, and 62% had influenza-like illness symptoms. Understanding the prevalence of asymptomatic and mildly symptomatic influenza cases is important for implementing effective influenza prevention strategies and enhancing symptom-based surveillance systems.

Background: Diagnostic methods for detecting infections caused by Bordetella species include culture, polymerase chain reaction (PCR), and serology. As the epidemiology of pertussis continues to evolve in the United States, we aimed to assess recent trends in provider testing practices and positivity for both Bordetella pertussis and Bordetella parapertussis.

Methods: Using deidentified data from a large US commercial laboratory, we identified Bordetella tests from 2019 through 2023. We described monthly trends in number of tests ordered by test type for culture, PCR (both nonpanel B. pertussis and B. parapertussis tests and those included as part of a respiratory panel), and serology, as well as percent positivity for serology and PCR. We also examined orders and positivity by patient age group and geographic region of the ordering provider.

Results: Among 527 206 tests, we identified 316 428 (60.1%) PCR tests, 204 480 (38.8%) serologic tests, and 5840 (1.1%) cultures. While most PCR tests were ordered as part of a respiratory panel (83.5%), only 215 (0.08%) were positive for B. pertussis. Nonpanel PCR positivity for B. pertussis was substantially higher but variable over the study period, ranging from 3% to 16%. We also observed a notable increase in B. parapertussis positivity on nonpanel PCR tests in the first half of 2023.

Conclusions: Both PCR and serology remain preferred diagnostic methods for providers. Despite their increasing popularity, B. pertussis positivity remained low for respiratory panels. Data from commercial laboratories can provide crucial insights into pertussis diagnostic trends over time.

Background: Vietnam, a high-burden tuberculosis (TB) country, experienced marked declines in TB notifications during the COVID-19 pandemic. We assessed the impact of pandemic-related disruptions on TB case detection and transmission using a dynamic transmission model calibrated to local demographic and epidemiological observations.

Methods: We developed an age-structured compartmental TB transmission model to estimate COVID-19's impact on TB in Vietnam. Four model assumptions reflecting reductions in detection and/or transmission were calibrated to notification data, with the best-fitting assumption used for future projections and to evaluate the effects of enhanced case detection scenarios.

Results: COVID-19 significantly disrupted TB services in Vietnam, resulting in an estimated 2000 additional TB episodes (95% credible interval [CrI]: 200-5100) and 1100 TB-related deaths (95% CrI: 100-2700) in 2021. By 2035, the cumulative impact of these disruptions could reach 22 000 additional TB episodes (95% CrI: 2200-63 000) and 5900 deaths (95% CrI: 600-16 600) by 2035. We predicted two hypothetical scenarios of enhancing TB case detection. Under the ambitious scenario, enhancing TB case detection could mitigate these potential impacts by preventing 17.8% of new TB episodes (95% CrI: 13.1%-21.9%) and 34.2% (95% CrI: 31.5%-37.0%) of TB-related deaths by 2035, compared with no enhancement.

Conclusions: COVID-19-related disruptions have hindered TB detection in Vietnam, likely causing long-term increases in new TB episodes and deaths. However, the uncertainty around these effects is considerable. Sustained investment in diagnostics, system resilience, and patient-centric policies has the potential to achieve benefits that are substantially larger than these pandemic-related setbacks.

Background: In the cervicovaginal environment, human papillomavirus (HPV) acquisition and cervical cancer progression are linked to non-Lactobacillus dominance, of which Atopobiaceae are key taxa. We hypothesize that Atopobiaceae modulates the cervicovaginal microenvironment to promote HPV persistence and progression to cancer. However, the extent to which Atopobiaceae impact the immunometabolic microenvironment is poorly understood.

Methods: We investigated Atopobiaceae in a cohort of primarily Hispanic and non-Hispanic White women who were HPV-negative (n = 20), HPV-positive (n = 31) without dysplasia, diagnosed with cervical dysplasia (n = 38), or newly diagnosed with invasive cervical carcinoma (n = 9). Microbiome data were integrated with clinical and demographic surveys, immunoproteomics, and metabolomics data.

Results: Atopobiaceae identified were Fannyhessea vaginae, Fannyhessea massiliense, Fannyhessea species type 2, Lancefieldella deltae, and an unclassified species. A higher prevalence of Atopobiaceae was observed in women who were Hispanic and had higher gravidity and parity. F. species type 2 and F. vaginae were observed with infections of high-risk HPV genotypes 31 and 52. Atopobiaceae were negatively correlated with Lactobacillus and positively correlated to Sneathia, Dialister, Anaerococcus, Prevotella, and Bifidobacterium/Gardnerella. Proinflammatory cytokines (IL-1α, IL-1β, IL-12, TNF-α), immune checkpoint proteins (PD-L1, LAG3), and cancer biomarkers (CEA, MIF, TRAIL) were positively associated with Atopobiaceae-rich profiles. Prooncogenic metabolites, including 4-hydroxybutyrate and sphingosine, were also elevated in women colonized by Atopobiaceae.

Conclusions: Our data implicate Atopobiaceae in lipid modulation, oxidative stress, inflammatory responses, and immune evasion, which may contribute to cancer. This study highlights a key family of pathogenic cervicovaginal bacteria that could be exploited to monitor HPV persistence and/or targeted to prevent HPV-mediated cancer.

Background: Serratia marcescens is an opportunistic AmpC β-lactamase-producing Enterobacterales associated with intensive care unit outbreaks, causing high morbidity and mortality. The spatiotemporal dynamics of Serratia species and their implications for hospital infection prevention and control remain understudied.

Methods: We prospectively identified patient culture specimens in a multihospital academic healthcare system from 2022 to 2024. We included first-time isolates of S. marcescens identified via culture and confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Isolates underwent whole-genome sequencing on the Illumina NextSeq 2000 platform. We queried assembled genomes using the Comprehensive Antibiotic Resistance Database to identify resistance genes and predict resistomes. We constructed a maximum-likelihood phylogenetic tree using GTDB-Tk-assigned taxonomies. We identified possible links between patients if there was a spatiotemporal overlap and the average nucleotide identity (ANI) of a sequence pair was > 99.0%. We collected relevant patient characteristics via retrospective chart review and analyzed data using descriptive statistics.

Results: Of 147 identified isolates, we included 125. Phenotypic testing suggested either inducible or derepressed AmpC expression in all isolates. Whole-genome sequencing found species-level discordance with MALDI-TOF MS in 64 (51.2%) isolates, suggesting the presence of multiple members of the recently described S. marcescens complex causing hospital- or community-associated infections. Only 1 isolate pair had a spatiotemporal link and ANI > 99.0%.

Conclusions: Between-patient transmission of S. marcescens complex outside of outbreaks is likely rare. Current MALDI-TOF MS-based identification methods are insufficient to identify S. marcescens complex and laboratory reporting should be modified to report only to the level of the complex.

Background: We estimated respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) illness incidences among pregnant women and examined the association between antenatal RSV illness and preterm birth and small-for-gestational-age (SGA) infant.

Methods: Pregnant women aged ≥18 years were contacted twice weekly until the end of pregnancy to identify illness episodes with ≥1 of the following: myalgia, cough, runny nose/nasal congestion, sore throat, or difficulty breathing. Midturbinate nasal swabs were collected and tested for RSV and hMPV by real-time reverse transcription polymerase chain reaction. Incidences were calculated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) comparing participants with and without RSV illnesses for preterm birth (live birth before 37 weeks' gestation) and SGA infant.

Results: Among 2764 participants, the median age was 29 years (IQR, 24-34), and the median enrollment gestational age was 10 weeks (IQR, 7-14). Overall, 71 (3%) and 29 (1%) cases of RSV and hMPV illnesses were identified, respectively. Among these, 30 (42%) and 10 (34%) participants sought medical care. Incidence rates per 10 000 pregnant woman-months were 57 (95% CI, 44-72) for RSV illnesses and 23 (95% CI, 16-33) for hMPV illnesses. Antenatal RSV illness in the third trimester conferred an increased risk of preterm birth (adjusted HR, 2.50; 95% CI, 1.04-6.00) but not SGA infant (adjusted HR, 0.79; 95% CI, .29-2.16).

Conclusions: Antenatal RSV illness was associated with some adverse antenatal outcomes. Pregnant women had a 0.4%-0.7% risk of RSV illness per pregnancy month, of which one-third resulted in medical visits.