Clinical Infectious Diseases最新文献

Background: Assessing variant-specific coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages.

Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 US states admitted 18 October 2023-9 March 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression.

Results: A total of 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4580 control patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% confidence interval [CI], 36.1-67.1%) against XBB lineage hospitalization and 32.7% (95% CI, 1.9-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR], .80; 95% CI, .46-1.38) and IMV or death (aOR, .69; 95% CI, .34-1.40) were not significantly different among JN compared with XBB lineage hospitalizations.

Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Background: Adults hospitalized with acute respiratory infections, including respiratory syncytial virus (RSV), often have multiple underlying conditions. Few data are available on the combined effect of conditions on risk of severe outcomes from RSV disease.

Methods: We enrolled adults hospitalized with RSV at 26 hospitals in 20 US states admitted January 2022-July 2024. Seventeen underlying conditions were selected after excluding those with rare prevalence (≤1%) or high pairwise correlation (≥0.7). We applied Bayesian profile regression to identify profiles of conditions associated with increased risk of RSV severe outcomes, stratifying among adults aged 18-59 and ≥60 years.

Results: We analyzed data from 1111 adults hospitalized with RSV (median [IQR] age, 66 [53-75] years). Among 397 adults aged 18-59 years, 2 profiles were identified: (1) minimal prevalence with fewer underlying conditions and a posterior median intensive care unit (ICU) admission risk of 21% (95% credible interval, 16%-25%) and (2) cardiorenal/diabetes with frequent heart failure, chronic kidney disease, diabetes, and increased ICU admission risk (37% [27%-48%]). Among 714 adults aged 60 years and older, 4 profiles were identified: (1) minimal prevalence (ICU admission risk, 22% [18%-26%]), (2) cardiorenal/diabetes (27% [21%-34%]), (3) hematologic malignancy and transplant receipt (12% [6%-21%]), and (4) chronic pulmonary disease with home oxygen dependence (44% [25%-66%]).

Conclusions: Distinct underlying condition profiles with varying risks of critical illness were observed among inpatients with RSV. These findings could support recognition of high-risk patients to inform RSV prevention strategies and suggest that the role of multimorbidity in severe RSV disease risk warrants further attention.

Background: Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis, but data on their accuracy, acceptability, and usability are limited.

Methods: We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with 3 methods: the Stool Processing Kit (SPK), the Simple One-Step method (SOS), and the Optimized Sucrose Flotation method (OSF). Children <15 years old with presumptive tuberculosis underwent sputum testing with Xpert Ultra and culture. We compared the accuracy of each method against a microbiological reference standard (tuberculosis if Xpert Ultra or culture positive) and a composite reference standard (tuberculosis if confirmed or unconfirmed tuberculosis). We surveyed laboratory staff to assess the acceptability and usability of the methods.

Results: We included 607 children, with a median age of 3.5 years (interquartile range, 1.3-7 years); 15.5% were human immunodeficiency virus positive. Against the microbiological reference standard, the sensitivities of SPK, SOS, and OSF were 36.9% (95% confidence interval, 28.6%-45.8%), 38.6% (17.2%-51.0%), and 31.3% (20.2%-44.1%), respectively, and the specificities, 98.2% (96.4%-99.3%), 97.3% (93.7%-99.1%), and 97.1% (93.3%-99%). The methods were acceptable and usable, but SOS was reported as most feasible to implement in a peripheral facility. Across methods, sensitivities increased among children who were culture positive (range, 55.0%-77.3%) and were low (13%-16.7%) against the composite reference standard. Adding stool Xpert Ultra increased sensitivity from 0% (OSF) to 11.8% (SPK/SOS), compared with sputum alone.

Conclusions: Stool processing methods for Xpert Ultra were acceptable and usable and performed similarly, with highest sensitivity among children with culture-positive tuberculosis.

Background: There is a lack of comprehensive, large cohort studies investigating the predictors for severity and hospitalization in human granulocytic anaplasmosis (HGA).

Methods: We conducted a retrospective cohort study including all cases of HGA identified by positive blood Anaplasma polymerase chain reaction (PCR) at the Mayo Clinic Laboratory, Rochester between 2011 and 2021. Multivariable logistic regression was performed to evaluate risk factors associated with hospitalization.

Results: A total of 465 cases were identified. Of those, 67% (n = 312) were managed in the outpatient setting. Hospitalized patients (n = 153, 33%) were more likely to be older (median age of 71 vs 61; P ≤ .001) and immunocompromised (17% vs 7%; P ≤ .001). The triad of leukopenia, thrombocytopenia, and transaminitis was observed in 24% of the cases, but was associated with risk of hospitalization (odds ratio [OR] 1.78, 95% confidence interval [CI]: 1.05-3.03; P ≤ .033). The presence of a coinfection did not impact mortality or hospitalization.

Conclusions: The risk factors for hospitalization in patients with HGA include altered mental status, higher absolute neutrophil count (ANC), advanced age, comorbidities, and immunosuppression. The classic hematological and biochemical profile may be absent in the majority of cases. Co-testing may be of higher benefit in select cases.

Background: Peripherally inserted central catheters (PICCs) have a 29% complication rate. This systematic review evaluated 25 interventions to prevent PICC-associated infectious and noninfectious complications in participants of all ages.

Methods: We searched electronic databases (MEDLINE, Embase, Cochrane Library, World Health Organization Global Index Medicus, CINAHL) and reference lists for randomized (RCTs) and nonrandomized controlled trials published between 1 January 1980-8 May 2024. We dually selected studies, assessed risk of bias, extracted data, and rated certainty of evidence (COE). We included single interventions of interest and combinations of at least 2 (bundle/multimodal). If 3 or more RCTs existed, we conducted Bayesian random-effects meta-analyses.

Results: Seventy-four studies met our eligibility criteria (60 evaluated single interventions, 14 bundle/multimodal), addressing 13 of 25 research questions. The majority were conducted in high-income countries; 36 focused on neonates. Evidence was very uncertain for 11 of the 13 research questions. Stronger COE showed that ultrasound-guided catheter insertion reduced phlebitis/thrombophlebitis in adults compared with non-ultrasound-guided (5 RCTs; risk ratio [RR], 0.19; 95% credible interval, .08-.50); silicone catheters increased phlebitis/thrombophlebitis compared with nonsilicone (1 RCT; RR, 2.00; 95% confidence interval [CI], 1.26-3.17). Bundle interventions decreased local infections (1 RCT; RR, 0.47; 95% CI, .31-.72) and phlebitis/thrombophlebitis in adults (1 RCT; RR, 0.35; 95% CI, .22-.56) compared with routine care.

Conclusions: Ultrasound-guided catheter insertion and nonsilicone catheters effectively prevented PICC complications. The evidence for other comparisons was too uncertain to draw conclusions, highlighting the urgent need for additional studies on prevention and control interventions.

Background: Ehrlichia and Rickettsia are tickborne pathogens capable of causing severe disease. Paired serological testing, involving both acute and convalescent samples, remains the primary method of diagnostic confirmation and source of surveillance data. Yet, few patients complete recommended testing algorithms.

Methods: We examined the demographic, clinical, and geographic factors associated with obtainment of convalescent samples for patients with suspected ehrlichiosis and spotted fever rickettsiosis using results from a large academic center in North Carolina between 2017 and 2020.

Results: More than 4400 patients underwent serological testing of an acute sample for Rickettsia (N = 4224) and Ehrlichia (N = 2339); however, only 15.0% (662/4415) had testing performed on a convalescent sample. Over the study period, the proportion of convalescent testing completed increased from 4% to 23% for Ehrlichia, 7% to 11% for Rickettsia, and 12% to 28% for both. A reactive test on the acute sample, undergoing testing for both pathogens, and proximity to a health facility were significantly associated with obtainment and testing of a convalescent sample. The presence of a reactive acute titer for Ehrlichia and Rickettsia had 8.3 (95% confidence interval, 6.3-10.9) and 8.2 (95% confidence interval, 6.5-10.3) times the probability of obtainment of a convalescent sample compared to nonreactive results, respectively.

Conclusions: Our findings suggest that clinicians' knowledge of tickborne disease testing practices, in addition to patient distance to health facilities, contribute to poor performance of testing completion. Moreover, these results highlight the need for more investment in public health surveillance and, ultimately, assays that are not dependent on convalescent testing.

Background: In 2010, the World Health Organization (WHO) increased the recommended doses of first-line tuberculosis (TB) drugs for children. In this systematic review, we aimed to determine the proportion of children who developed adverse events (AEs) on first-line TB treatment and determine whether a change in toxicity was observed with WHO 2010 dosing.

Methods: We searched MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, and ClinicalTrials.gov for studies that reported AEs for children and adolescents aged ≤19 years with TB disease receiving first-line medications. A meta-analysis of proportions was performed to generate pooled proportions of AEs. The protocol was registered with the International Prospective Register of Systematic Reviews.

Results: Of forty studies comprising 5021 participants, 682 (13.6%) participants experienced 712 AEs; 60 (1.2%) participants experienced a change in therapy due to AEs. The proportion of children with any AE was significantly higher with WHO 2010 dosing (26%; 95% confidence interval [CI], 18%-34%) compared with pre-WHO 2010 dosing (8%, 95% CI, 4%-15%), as was the proportion of children who developed severe AEs. There was no significant difference in hepatotoxicity before and after 2010 dosing recommendations; however, significant increases in hepatotoxicity were seen in several subgroups with 2010 dosing. There was substantial heterogeneity between studies; none were at high risk of bias.

Conclusions: Higher-dose regimens in children were associated with increased AEs, raising caution for further dose increases and necessitating additional study of treatment tolerability. These findings are limited by publication bias in observational trials.