Clinical Infectious Diseases最新文献

Background: Interferon γ release assays (IGRAs) are widely used for diagnosis of latent tuberculosis infection. However, with repeated testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation.

Methods: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and participant characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors.

Results: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% confidence interval [CI], 6.1%-8.5%) or 22.8% (20.1%-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (95% CI, 35.7%-56.4%) or 19.6% (9.2%-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [95% CI, .1%-3.5%]). IGRA results in the borderline-positive or borderline-negative range were associated with increased risk of conversion or reversion (pooled odds ratio [OR] for conversion, 4.15 [95% CI, 3.00-5.30]; pooled OR for reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (OR, 0.70 [95% CI, .56-.84]), cigarette smoking with decreased risk of reversion (0.44 [.06-.82]), and female sex with decreased risk of either conversion or reversion (OR for conversion, 0.66 [.58-.75]; OR for reversion, 0.46 [.31-.61]).

Conclusions: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis-preventive treatment. Retesting of people with indeterminate results is probably not indicated, because indeterminate results seldom revert to positive.

Background: Substantial efforts focus on monitoring and reducing delays in antibiotic treatment for sepsis, but little has been done to characterize the balancing measure of sepsis overtreatment. We aimed to establish preliminary validity and usefulness of electronic health record (EHR) data-derived criteria for sepsis overtreatment surveillance (SEP-OS).

Methods: We evaluated adults with potential sepsis (≥2 Systemic Inflammatory Response Syndrome criteria within 6 hours of arrival) presenting to the emergency department of 12 hospitals, excluding patients with shock. We defined SEP-OS as the proportion of patients receiving rapid IV antibiotics (≤3 hours) who did not ultimately meet the Centers for Disease Control Adult Sepsis Event "true sepsis" definition. We evaluated the frequency and characteristics of patients meeting overtreatment criteria and outcomes associated with sepsis overtreatment.

Results: Of 113 764 eligible patients, the prevalence of sepsis overtreatment was 22.5%. The measure met prespecified criteria for reliability, content, construct, and criterion validity. Patients classified by the SEP-OS overtreatment criteria had higher median antibiotic days (4 days [IQR, 2-5] vs 1 day [1-2]; P < .01), longer median length of stay (4 days [2-6] vs 3 days [2-5]; P < .01), higher hospital mortality (2.4% vs 2.1%; P = .01), and higher frequency of Clostridioides difficile infection within 6 months of hospital discharge (P < .01) compared with "true negative" cases.

Conclusions: We developed a novel, valid EHR metric for clinical surveillance of sepsis overtreatment. Applying this metric to a large cohort of potential sepsis patients revealed a high rate of overtreatment and provides a useful tool to inform sepsis quality-improvement targets.

Background: An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed.

Methods: A prospective evaluation of the Cepheid GeneXpert Mycobacterium tuberculosis Host Response cartridge (Xpert-MTB-HR), a prototype blood-based host response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to 3 reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (aged 10-24 years).

Results: A total of 497 participants, aged 6-83 years, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95% confidence interval [CI], 28%-37%) compared to Xpert MTB/RIF Ultra, 29% (95% CI, 25%-34%) compared to a bacteriological confirmation, and 22% (95% CI, 18%-26%) compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95% CI, 74%-89%) compared to Xpert MTB/RIF Ultra, 84% (95% CI, 75%-90%) compared to a bacteriological confirmation, and 54% (95% CI, 44%-64%) compared to a composite clinical diagnosis.

Conclusions: While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.

Background: Dengue is an increasing threat to global health. This exploratory analysis evaluated the immunogenicity, safety, and vaccine efficacy (VE) of a live-attenuated tetravalent dengue vaccine (TAK-003) in participants enrolled in the phase 3 DEN-301 trial (NCT02747927), stratified by baseline age (4-5 years, 6-11 years, or 12-16 years).

Methods: Participants were randomized 2:1 to receive 2 doses of TAK-003, administered 3 months apart, or placebo. Dengue serostatus was evaluated at enrolment. VE against virologically confirmed dengue (VCD) and hospitalized VCD; immunogenicity (geometric mean titers [GMTs]); and safety were evaluated per age group through ∼4 years postvaccination.

Results: VE against VCD across serotypes was 43.5% (95% confidence interval [CI]: 25.3%, 57.3%) for 4-5 year-olds; 63.5% (95% CI: 56.9%, 69.1%) for 6-11 year-olds, and 67.7% (95% CI: 57.8%, 75.2%) for 12-16 year-olds. VE against hospitalized VCD was 63.8% (95% CI: 21.1%, 83.4%), 85.1% (95% CI: 77.1%, 90.3%), and 89.7% (95% CI: 77.9%, 95.2%), for the 3 age groups, respectively. GMTs remained elevated against all 4 serotypes for ∼4 years postvaccination, with no evident differences across age groups. No clear differences in safety by age were identified.

Conclusions: This exploratory analysis shows TAK-003 was efficacious in dengue prevention across age groups in children and adolescents 4-16 years of age living in dengue endemic areas. Relatively lower VE in 4-5 year-olds was potentially confounded by causative serotype distribution, small sample size, and VE by serotype, and should be considered in benefit-risk evaluations in this age group.