This study developed a pharmacokinetic model and web-based tool to distinguish true invasive aspergillosis from false positives caused by contaminated fluids. By analyzing galactomannan kinetics, false positives were identified within 24 hours, improving diagnostic accuracy and aiding clinicians in early decision making while minimizing unnecessary interventions.
Textbooks remain a primary source of reference and education for many health care professionals and students. This study assessed the mycology content in leading internal medicine and infectious diseases textbooks, revealing significant gaps across multiple areas. Infectious diseases textbooks demonstrated better coverage compared with internal medicine textbooks, highlighting the need for improved educational resources.
Background: In May 2022, mpox (formerly monkeypox) began spreading globally through LGBTQ+ sexual networks. By August 2022, New York City (NYC) became the global epicenter of the mpox outbreak, with the highest number of cases reported in the United States. Here, we quantify the mpox vaccination effort, focusing on flexible and community-responsive mobile vaccination.
Methods: We describe an on-site mpox vaccination strategy at commercial sex venues, nightlife venues, and pride and health centers, during August 1-November 15, 2022. Data were collected on doses, demographics, and event size to determine and evaluate vaccine uptake.
Results: The on-site vaccination strategy resulted in 3358 JYNNEOS doses administered at 363 events at 58 locations, including 22 events at 2 commercial sex venues. Commercial sex venues in New York City closed at the height of the mpox epidemic. We show high uptake of the JYNNEOS vaccine at commercial sex venues, with as many as 60% of attendees of 1 event receiving a JYNNEOS vaccine dose on site. This was possible after New York City health agencies responded to community demand for second doses. Messaging about the importance and availability of vaccination at these parties was community-led. JYNNEOS vaccination via mobile clinics demonstrated less racial and geographic disparity compared with nonmobile vaccinations. We show no increase in mpox cases as commercial sex venues reopened with vaccination on site.
Conclusions: These results demonstrate the success of a community-led rapid response to an emergent mpox outbreak, including at places where people meet for sex.
Background: There were limited data on tuberculosis (TB) epidemiology and outcomes among older adults in the United States. We analyzed TB epidemiology and outcomes among New York City residents to identify opportunities for prevention and improved outcomes among older adults.
Methods: We used New York City TB surveillance data to describe TB incidence, patient characteristics, and treatment outcomes comparing older (≥65 years) and younger (18-64 years) adults. Cox proportional hazard models were used to assess characteristics associated with death.
Results: During 2001-2022, overall TB incidence declined from 18 to 7 cases per 100 000 population. Of 5577 TB cases during 2011-2020, 1360 (24%) were among older adults. Among older adults with TB, 86% were born outside the United States (median of 24 years in United States at diagnosis), 8% had lived in long-term care facilities, and 5% died before starting TB treatment. Hazard ratio (HR) of death among adults aged 65-74 years during TB treatment was 7.19 (95% confidence interval [CI], 4.56-11.34) compared to adults aged 18-44 years. Among older adults, those with a history of living in long-term care (HR, 2.57; 95% CI, 1.74-3.80) or hepatitis B or C (HR, 1.86; 95% CI, 1.09-3.15) had a higher hazard of death during treatment.
Conclusions: Efforts to prevent TB among older New Yorkers by identifying and treating latent TB could focus on long-term care facility residents. Educating providers regarding early diagnosis of TB and comorbidities associated with poor treatment outcomes might help prevent onward transmission and TB-associated mortality in this age group.
Background: Weight gain associated with integrase strand transfer inhibitors (INSTIs) is well documented. However, recent reports suggest that the observed weight gain among persons who switch to INSTIs may be associated with their preswitch regimen.
Methods: We conducted retrospective analyses of persons with HIV on antiretroviral therapy who switched to a second-generation INSTI-containing regimen (bictegravir/dolutegravir) at the Duke Adult Infectious Diseases Clinic (Durham, NC, USA) between 2014 and 2021. The outcome was weight change, operationalized as percent weight change, absolute weight change (kg), gaining ≥5% of preswitch weight, and gaining ≥10% of preswitch weight. The primary exposure was preswitch regimen.
Results: Our analysis included 750 persons. Cohort demographics were as follows: mean age (SD) 51 (11) years, 30% female at birth, 58% Black, 4% Hispanic ethnicity. At regimen switch, the mean CD4 count was 701 cells/mm3, and 68% had a viral load ≤20 copies/cc. Persons with preswitch regimens containing efavirenz had higher odds of gaining ≥5% body weight (odds ratio [OR], 1.62, 95% CI, 1.13-2.32) and ≥10% body weight (OR, 1.68; 95% CI, 1.02-2.73) after regimen switch, adjusted for age, sex, race, ethnicity, and preswitch body mass index. Persons with preswitch regimens containing tenofovir disoproxil (TDF) also had higher odds of gaining ≥5% body weight (OR, 1.64; 95% CI, 1.17-2.30).
Conclusions: Preswitch regimens containing efavirenz and TDF were associated with significant weight gain after switching to INSTI-based regimens. Our findings support the hypothesis that the weight gain observed with switching to INSTI-based regimens could be driven by stopping medications with weight-suppressing properties.
Background: Phage therapy is being reconsidered as a valuable approach to combat antimicrobial resistance. We recently established a personalized phage therapy pipeline in healthy volunteers, where therapeutic phages were isolated from individuals' skin microbiota. In this study, we aim to validate this pipeline in end-stage heart failure patients supported by left ventricular assist devices (LVADs), focusing on phages targeting Staphylococcus epidermidis, a common pathogen responsible for LVAD infections.
Methods: Over a 2.5-year period, 45 LVAD patients were consistently sampled at their driveline exit sites and foreheads. S epidermidis strains from patients' foreheads were used to amplify patient-specific phages. Newly isolated phages were characterized and tested against S epidermidis isolates (n = 42) from the patient cohort. The virulent phage vB_SepS_BE22, isolated from a patient with a driveline infection, was further tested for its bactericidal activity against S epidermidis biofilms ex vivo with rifampicin on driveline biofilms.
Results: S epidermidis was detected in 32 patients, 3 of whom had driveline infections. Phages were isolated from 8 patients, 6 of which were unique and exhibited narrow host ranges, infecting 19%-52% of S epidermidis strains. vB_SepS_BE22, isolated from patient ID25's microbiota, was the only phage that specifically killed S epidermidis clones linked to a patient's infection. vB_SepS_BE22 also reduced bacterial loads in exponential and stationary phase cultures, as well as in biofilms on drivelines when combined with rifampicin.
Conclusions: This study validated a personalized phage therapy approach, where phages from a patient's own microbiota can be used in chronic infection settings as therapeutic agents.
Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health-funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021 and February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research participants with prior SARS-CoV-2 infection, the mean age (standard deviation) was 65.8 (12.1), 61% were women, and 42.8% self-reported membership in a race/ethnicity minority group. The proportion of participants reactive to nucleocapsid peaked at 69% by 4 months after infection and waned to only 44% ≥12 months after infection. Higher anti-nucleocapsid antibody response was associated with older age, Hispanic or American Indian Alaskan Native (vs White) race/ethnicity, lower income, lower education, former smoking, and higher anti-spike antibody levels. Asian race (vs White) and vaccination (even after infection) were associated with lower nucleocapsid reactivity. Neither vaccine manufacturer nor common cardiometabolic comorbidities were not associated with anti-nucleocapsid response. These findings inform the underlying immunobiology of adaptive immune response to infection, as well as the potential utility of anti-nucleocapsid antibody response for clinical practice and COVID-19 serosurveillance.
[This corrects the article DOI: 10.1093/ofid/ofae496.].
Background: Few studies have assessed tuberculosis (TB) disease incidence and risk in a large US-based cohort with long-term longitudinal follow-up.
Methods: In a retrospective cohort study from 2004 to 2022, we assessed risk of incident microbiologically confirmed TB disease using Cox proportional hazards models. Primary exposures were (1) nativity and (2) high-risk medical conditions for progression to TB disease.
Results: Among 4 761 427 adults with 35 591 565 person-years (PY) of follow-up, 12.3% were born in TB-endemic countries and 5.5% had a high-risk medical condition. In all, 1463 had incident TB disease (incidence rate, 4.11/100 000PY), with persons born in TB-endemic countries (incidence rate [IR], 17.6/100 000PY; 95% CI, 16.4-18.7/100 000PY) having higher TB disease rates than US-born persons (IR, 1.27/100 000PY; 95% CI, 1.09-1.44/100 000PY), with an adjusted hazard ratio (aHR) of 15.3 (95% CI, 13.2-17.9). Persons with high-risk conditions (IR, 11.3/100 000PY; 95% CI, 10.0-12.6/100 000PY) had higher TB disease rates than persons without any conditions (IR, 2.63/100 000PY; 95% CI, 2.43-2.82/100 000PY). Persons with HIV infection (aHR, 3.77; 95% CI, 2.7-3.89), hematologic malignancy (aHR, 1.62; 95% CI, 1.17-2.22), diabetes mellitus (aHR, 2.85; 95% CI, 2.53-3.20), end-stage renal disease (aHR, 2.84; 95% CI, 2.07-3.20), and those who had received corticosteroids (aHR, 1.39; 95% CI, 1.10-1.77) or other immunosuppressants (aHR, 2.37; 95% CI, 1.73-3.24) had significantly increased TB disease risk compared with persons without those conditions. Persons born in TB-endemic countries accounted for 79.1% all TB cases among persons with high-risk conditions.
Conclusions: Persons born in TB-endemic countries are the largest group and have the highest risk for developing TB disease in the United States, and thus should be prioritized for LTBI screening and treatment.
Background: Cardiovascular and metabolic comorbidities are common in people with HIV (PWH) and are linked to chronic inflammation and immune activation. We assessed the effects of semaglutide on plasma markers of immune activation/inflammation that are known to be increased in PWH and are associated with morbidity and mortality in this population.
Methods: We conducted a single-site, randomized, double-blinded, placebo-controlled trial of virologically suppressed, nondiabetic PWH ≥18 years of age on stable antiretroviral therapy with body mass index ≥ 25 kg/m2, increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after antiretroviral therapy initiation (clinicaltrials.gov: NCT04019197). Participants were randomized 1:1 to 32 weeks of semaglutide (8-week titration + 24 weeks of 1.0 mg weekly subcutaneous injection) or matching placebo. Signed-rank tests were used to determine changes over 32 weeks in soluble markers and cellular phenotypes of inflammation/immune activation within groups; semaglutide effects were assessed using linear or quantile regression analyses.
Results: A total of 108 participants were enrolled and evenly randomized to semaglutide versus placebo. Eight (15%) in each group withdrew prematurely. Thirty-two weeks of semaglutide treatment reduced baseline levels of C-reactive protein, interleukin-6, and soluble CD163 (all P < .02) and trended to reduce levels of sCD14 (P = .08). Circulating monocyte proportions and T-cell phenotypes were not altered by semaglutide.
Conclusions: In this randomized controlled trial of semaglutide in PWH, we report significant decreases in markers of inflammation that are associated with morbidity and mortality in this population. These results add to the growing literature demonstrating the anti-inflammatory effects of semaglutide. Further studies in PWH are warranted.
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