Open Forum Infectious Diseases最新文献

Diagnostic algorithms for syphilis are based on serology. However, with the advent of immunosuppressive therapies, these algorithms may fail. We report a case of an individual with multiple sclerosis on treatment with ofatumumab and secondary syphilis with visual and auditory systems involvement and persistent negative treponemal and nontreponemal tests.

Single-dose doxycycline after high-risk tick bites can prevent Lyme disease, which disproportionately affects children. We described single-dose doxycycline dispensings in an outpatient cohort in the United States. During 2010-2020, a total of 427 105 patients received ≥1 dispensing(s); most were aged ≥65 years. Lyme disease postexposure prophylaxis may be underprescribed for some groups, including children.

Background: Globally, Creutzfeldt-Jakob disease (CJD) affects one in one million people annually, but there is a paucity of recent Canadian data. This study summarizes epidemiology trends and diagnostic timelines of laboratory-confirmed CJD cases in three tertiary Ontario hospitals.

Method: Using laboratory information systems, we identified 30 patients with a laboratory-confirmed CJD diagnosis between 2012 and 2022 at three major tertiary hospitals in Ontario. Retrospective chart reviews were then completed.

Results: Patients had a mean of 2.2 hospital visits (SD, 1.2) prior to being admitted for testing. The most common symptom presentations included loss of coordination (63.3%), behavioral changes (60%), progressive mobility loss (53.4%), memory loss (50.0%), and involuntary movements (50.0%). Magnetic resonance imaging findings showed potential CJD in 76.7% of cases, and 56.7% exhibited periodic sharp wave complexes characteristic of CJD on electroencephalogram. The mean duration from symptom onset to microbiologic testing was 91 days (SD, 90.7). End-point quaking-induced conversion (EP-QuIC) testing of cerebrospinal fluid was positive in 90.0% of patients, while 83.3% tested positive for 14-3-3 on enzyme-linked immunosorbent assay. Elevated cerebrospinal fluid 14-3-3 levels significantly correlated with shorter duration from symptom onset to death (R ² = 0.71, F = 19.55, P = .0022). Post-diagnosis, 46.7% of patients were discharged home, 16.6% were transferred to external palliative care or hospice facilities, and 36.7% died during admission. The mean time from symptom onset to death was 121 days (SD, 120.7), and from diagnosis to death 35 days (SD, 83.9).

Conclusions: This study highlights the importance of early CJD consideration and laboratory testing when appropriate neurologic symptoms are present.

The neonatal nasal microbiota may help protect neonates in the neonatal intensive care unit from pathogen colonization and infection. This preliminary study characterized the biodiversity of nasal microbiota comparing neonates in the neonatal intensive care unit and their mothers, highlighting the potential of strain sharing between mother-neonate pairs.

Background: Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (Mtb) by mechanisms that remain to be fully explained. We evaluated the association between Mtb sensitization and T2DM and, via mediation analysis, the extent to which it is mediated by insulin resistance and/or β-cell failure.

Methods: Adults were assessed for T2DM by fasting plasma glucose, 2-hour oral glucose tolerance testing, and hemoglobin A_1c; β-cell dysfunction and insulin resistance by homoeostasis model assessment 2; and Mtb sensitization by tuberculin skin testing. Associations between Mtb sensitization and T2DM were modeled with probit regression and decomposed into indirect effects of β-cell dysfunction and insulin resistance. Analyses were adjusted for sociodemographic, behavioral, and clinical characteristics.

Results: We included 1843 adults. Individuals with Mtb sensitization were older than those without Mtb (median [IQR], 54 [39-64] vs 47 [33-62] years). As compared with being uninfected, Mtb sensitization was associated with T2DM (adjusted absolute risk difference, 9.34% [95% CI, 2.38%-15.0%]; P < .001) and increased insulin resistance (adjusted median difference, 0.16 [95% CI, .03-.29]; P = .014) but not β-cell dysfunction (adjusted median difference, -3.1 [95% CI, -10.4 to 4.3]; P = .42). In mediation analyses, insulin resistance mediated 18.3% (95% CI, 3.29%-36.0%; P = .020) of the total effect of the association between Mtb sensitization and T2DM.

Conclusions: Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Notwithstanding, our findings suggest that exposure to Mtb may be a novel risk factor for T2DM, likely driven by an increase in insulin resistance.

Background: It is unknown whether ChatGPT provides quality responses to infectious diseases (ID) pharmacotherapy questions. This study surveyed ID pharmacist subject matter experts (SMEs) to assess the quality of ChatGPT version 3.5 (GPT-3.5) responses.

Methods: The primary outcome was the percentage of GPT-3.5 responses considered useful by SME rating. Secondary outcomes were SMEs' ratings of correctness, completeness, and safety. Rating definitions were based on literature review. One hundred ID pharmacotherapy questions were entered into GPT-3.5 without custom instructions or additional prompts, and responses were recorded. A 0-10 rating scale for correctness, completeness, and safety was developed and validated for interrater reliability. Continuous and categorical variables were assessed for interrater reliability via average measures intraclass correlation coefficient and Fleiss multirater kappa, respectively. SMEs' responses were compared by the Kruskal-Wallis test and chi-square test for continuous and categorical variables.

Results: SMEs considered 41.8% of responses useful. Median (IQR) ratings for correctness, completeness, and safety were 7 (4-9), 5 (3-8), and 8 (4-10), respectively. The Fleiss multirater kappa for usefulness was 0.379 (95% CI, .317-.441) indicating fair agreement, and intraclass correlation coefficients were 0.820 (95% CI, .758-.870), 0.745 (95% CI, .656-.816), and 0.833 (95% CI, .775-.880) for correctness, completeness, and safety, indicating at least substantial agreement. No significant difference was observed among SME responses for percentage of responses considered useful.

Conclusions: Fewer than 50% of GPT-3.5 responses were considered useful by SMEs. Responses were mostly considered correct and safe but were often incomplete, suggesting that GPT-3.5 responses may not replace an ID pharmacist's responses.

Background: A serum-free, highly purified Vero rabies vaccine-next generation (PVRV-NG2) is under development. We conducted a phase III trial to describe the safety and immunogenicity profile of PVRV-NG2 compared with those of licensed purified Vero rabies vaccine (PVRV) in a simulated rabies postexposure prophylaxis (PEP) Zagreb regimen in Thailand.

Methods: Healthy adults aged ≥18 years (n = 201) were randomized in a 2:1 ratio to receive PVRV-NG2 or PVRV in a rabies PEP Zagreb (days 0, 7, 21 [2-1-1]) regimen, with concomitant human rabies immunoglobulin (HRIG) at day 0. Immunogenicity end points included the proportion of participants with rabies virus-neutralizing antibody (RVNA) titers ≥0.5 IU/mL at days 0, 14, and 35. Safety outcomes were also assessed.

Results: A total of 199 participants completed the study (PVRV-NG2 n = 133, PVRV n = 66). In the PVRV-NG2 group and PVRV group, respectively, 91.0% (95% CI, 84.1%-95.6%) and 94.6% (95% CI, 85.1%-98.9%) had RVNA titers ≥0.5 IU/mL at day 14, increasing to 100% (95% CI, 96.8%-100%) and 100% (95% CI, 93.5%-100%) by day 35. The vaccines had similar safety profiles, and there were no safety concerns.

Conclusions: PVRV-NG2 showed acceptable safety and immunogenicity profiles when co-administered with HRIG in a simulated PEP Zagreb regimen in healthy adults in Thailand.

Background: Little is known about outcomes from cancer chemotherapy--associated infections in sub-Saharan Africa. Accordingly, among patients with cancer admitted with postchemotherapy infection in Mbarara, Uganda, we aimed to determine (1) the 30-day case fatality rate, (2) factors associated with mortality rate, and (3) clinical risk score performance.

Methods: We enrolled participants aged ≥18 years if they (1) received cancer chemotherapy within the past 30 days, (2) were admitted to the oncology ward, and (3) were prescribed intravenous antibiotics. We used Cox proportional hazards regression to determine predictors of death at 30 days and calculated the area under the receiver operating characteristic curve (AUC) for each clinical risk score.

Results: Among 150 participants, 67 (45%) were female, and the median (interquartile range) age was 56 (43-66) years. Esophageal cancer (18%) and pneumonia (42%) were the most common cancer and infection, respectively. Death occurred within 30 days in 63 participants (42%). Quick Sequential Organ Failure Assessment (qSOFA) score ≥2 (adjusted hazard ratio, 2.51 [95% confidence interval, 1.42-4.44]; P = .001), and Universal Vital Assessment (UVA) score >4 (2.13 [.08-4.18, P = .03) were independently associated with death at 30 days. An Eastern Cooperative Oncology Group (ECOG) score ≥3 was similarly independently associated with death at 30 days in the qSOFA and UVA models. The AUCs for qSOFA and UVA scores were 0.70 (95% confidence interval, .63-.79) and 0.72 (.64-.80), respectively.

Conclusions: In participants with postchemotherapy infection in Mbarara, Uganda, the case fatality rate was high. ECOG, qSOFA, and UVA scores were associated with death at 30 days.

Background: The Grading Recommendations, Assessment, Development, and Evaluations (GRADE) framework is widely applied in clinical guidelines to facilitate transparent evidence evaluation. While developing Infectious Diseases Society of America (IDSA) guidelines on the management of patients with coronavirus disease 2019 (COVID-19), panel members suggested developing and implementing a visual aid to enable quicker identification of key information by providers at bedside seeking guidance.

Methods: We conducted a mixed-methods study evaluating the usability of a newly designed infographic/icon using a survey and focus groups. The survey incorporated a simulated COVID-19 IDSA guideline with and without the icon, followed by comprehension questions. Focus group discussions provided qualitative feedback on the GRADE methodology and icon usability.

Results: The survey was returned by 289 health care providers. There was no statistical difference in the correct response rates between icon-aided and non-icon-aided guideline questions (McNemar's chi-square test, P > .1 for both questions). Interactions with the icon notably increased the time taken and number of clicks required to respond to the first question (Wilcoxon signed-rank test, P < .01). In contrast, response time did not differ between versions for the second question (P = .38). Most subjects (85%) indicated that the icon improved the readability of the guidelines. A focus group follow-up suggested alternative designs for the icon.

Conclusions: This study highlights the promise of iconography in clinical guidelines, although the specific icons tested did not measurably improve usability metrics. Future research should focus on icon design and testing within a formal usability framework, considering the impact of GRADE language on user experience.