Plasma Microbial Cell-Free DNA Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections.

BACKGROUND: Nearly half of all pediatric musculoskeletal infections (MSKIs) are culture negative. Plasma microbial cell-free DNA (mcfDNA) sequencing is noninvasive and not prone to the barriers of culture. We evaluated the performance of plasma mcfDNA sequencing in identifying a pathogen, and examined the duration of pathogen detection in children with MSKIs. METHODS: We conducted a prospective study of children, aged 6 months to 18 years, hospitalized from July 2019 to May 2022 with MSKIs, in whom we obtained serial plasma mcfDNA sequencing samples and compared the results with cultures. RESULTS: A pathogen was recovered by culture in 23 of 34 (68%) participants, and by initial mcfDNA sequencing in 25 of 31 (81%) participants. Multiple pathogens were detected in the majority (56%) of positive initial samples. Complete concordance with culture (all organisms accounted for by both methods) was 32%, partial concordance (at least one of the same organism(s) identified by both methods) was 36%, and discordance was 32%. mcfDNA sequencing was more likely to show concordance (complete or partial) if obtained prior to a surgical procedure (82%), compared with after (20%), (RR 4.12 [95% CI 1.25, 22.93], p = .02). There was no difference in concordance based on timing of antibiotics (presample antibiotics 60% vs no antibiotics 75%, RR 0.8 [95% CI 0.40, 1.46], p = .65]). mcfDNA sequencing was positive in 67% of culture-negative infections and detected a pathogen for a longer interval than blood culture (median 2 days [IQR 1, 6 days] vs 1 day [1, 1 day], p < .01). CONCLUSIONS: Plasma mcfDNA sequencing may be useful in culture-negative pediatric MSKIs if the sample is obtained prior to surgery. However, results must be interpreted in the appropriate clinical context as multiple pathogens are frequently detected supporting the need for diagnostic stewardship.

Identifying Patient-Centered Outcomes for Caregivers and Children With Musculoskeletal Infections.

Background: Musculoskeletal infections (MSKI), including osteomyelitis and septic arthritis, are among the most common invasive infections in children and have the potential to cause significant morbidity. Guidelines have been developed to optimize care based on clinician-developed endpoints. Patient-centered outcomes have not been defined for children with MSKI. This study identified outcomes most important to caregivers and patients with MSKI. Methods: This was a single-center prospective qualitative study of children 6 months to 18 years of age hospitalized with MSKI from November 2019 to September 2021. Using design-research methods, patients and caregivers participated in interviews and/or completed journals to describe their experiences during acute infection and recovery from MSKI. Results: A total of 51 patient/caregivers were approached to participate in the study, 35 of whom declined to participate, resulting in 8 interviews conducted and 14 journals collected from 16 patient/caregivers. From these, a journey map was created highlighting points of stress during the onset of symptoms, through hospitalization, and returning home with new challenges. In addition, patient-centered outcomes were identified. For caregivers, these included managing mental health, managing responsibilities, and receiving support. Both caregivers and patients shared the importance of understanding of treatment plans and responsibilities. For patients, improving mental and physical health was important. Conclusions: Management of children with MSKI is complex and requires a multidisciplinary team approach. Validation of the outcomes identified and development of a measurement tool are needed. Addressing the patient-centered outcomes we identified in this study can greatly improve the holistic care of children with MSKI.

Increasing fire frequency and severity will increase habitat loss for a boreal forest indicator species.

Climate change will lead to more frequent and more severe fires in some areas of boreal forests, affecting the distribution and availability of late-successional forest communities. These forest communities help to protect globally significant carbon reserves beneath permafrost layers and provide habitat for many animal species, including forest-dwelling caribou. Many caribou populations are declining, yet the mechanisms by which changing fire regimes could affect caribou declines are poorly understood. We analyzed resource selection of 686 GPS-collared female caribou from three ecotypes and 15 populations in a ~600,000 km2 region of northwest Canada and eastern Alaska. These populations span a wide gradient of fire frequency but experience low levels of human-caused habitat disturbance. We used a mixed-effects modeling framework to characterize caribou resource selection in response to burns at different seasons and spatiotemporal scales, and to test for functional responses in resource selection to burn availability. We also tested mechanisms driving observed selection patterns using burn severity and lichen cover data. Caribou avoided burns more strongly during winter relative to summer and at larger spatiotemporal scales relative to smaller scales. During the winter, caribou consistently avoided burns at both spatiotemporal scales as burn availability increased, indicating little evidence of a functional response. However, they decreased their avoidance of burns during summer as burn availability increased. Burn availability explained more variation in caribou selection for burns than ecotype. Within burns, caribou strongly avoided severely burned areas in winter, and this avoidance lasted nearly 30 years after a fire. Caribou within burns also selected higher cover of terrestrial lichen (an important caribou food source). We found a negative relationship between burn severity and lichen cover, confirming that caribou avoidance of burns was consistent with lower lichen abundance. Consistent winter avoidance of burns and severely burned areas suggests that caribou will experience increasing winter habitat loss as fire frequency and severity increase. Our results highlight the potential for climate-induced alteration of natural disturbance regimes to affect boreal biodiversity through habitat loss. We suggest that management strategies prioritizing protection of core winter range habitat with lower burn probabilities would provide important climate-change refugia for caribou.