To evaluate the presence of human T-lymphotropic virus type 1 (HTLV-1) infection in isolated rural communities in the southern Andes of Peru. We conducted a cross-sectional study in five communities located in three provinces in Ayacucho, Peru. The five communities are located at >3000 meters above sea level and are mainly rural, and more than 85% of the population speaks Quechua. Volunteers aged 12 years and older were included. Clinical and epidemiological data were collected, along with a blood sample for serological testing. We included 397 participants; their median age was 41 years (interquartile range 31-57 years) and 69% were women. According to our definitions, 98% were of Quechua origin. HTLV-1 was diagnosed in 11 people: 0/164 in Cangallo, 3/154 (2%) in Vilcashuaman, and 8/79 (10%) in Parinacochas. There were no cases of HTLV-2. All the HTLV-1-positive participants were born in Ayacucho and were of Quechua origin; they ranged in age from 29 to 87 years (median 56 years) and 10/11 were women. Ten were apparently healthy, and one woman was diagnosed with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Three out of 11 had a family member with a lower limb impairment compatible with HAM/TSP. The fact that HTLV-1 infection was present in two out of three provinces suggests that HTLV-1 could be highly endemic in the southern Andes in the Quechua population.
Background: Respiratory syncytial virus (RSV) is a significant health risk for adults aged 18–59 years with chronic medical conditions. Methods: This ongoing, randomized, double-blind phase 3 trial evaluates safety and immunogenicity of the RSV vaccine, mRNA-1345, in adults aged 18–59 years at increased risk for RSV-associated lower respiratory tract disease (LRTD). Participants received a single 50-µg (licensed dose) or 30-µg dose. Co-primary immunogenicity objectives were to demonstrate noninferiority of day 29 RSV-A/B neutralizing antibody (nAb) geometric mean titers (GMTs) for the 50-μg dose compared with those observed in adults aged ≥60 years from the phase 3 pivotal efficacy trial. The other primary objective was to evaluate safety and tolerability. Results: A total of 999 participants received mRNA-1345 (50 µg, n = 502; 30 µg, n = 497). Most solicited adverse reactions (ARs) were mild to moderate with a median duration of 2 days. Day 29 nAb GMTs in the 50-µg group met noninferiority criteria: RSV-A GMT ratio (GMR), 1.2 (95% confidence interval [CI], 1.1–1.3); RSV-B GMR, 1.1 (95% CI, 1.0–1.2). Noninferiority was also demonstrated for seroresponse rate differences: RSV-A, 11.8% (95% CI, 7.8–15.5); RSV-B, 10.8% (95% CI, 5.9–15.6). Immune responses were consistent across subgroups and remained above baseline through day 181. Conclusions: In adults aged 18–59 years at increased risk for RSV-LRTD, a 50-µg dose of mRNA-1345 was well tolerated and elicited RSV-A and RSV-B nAb responses noninferior to those observed in older adults in the pivotal study, supporting inference of efficacy in this population. Clinical Trials Registration: NCT06067230
16 February 2020 in American Journal of Transplantation
Hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case‐control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case‐control study identified prior history of CDI (OR 2.6, 95% CI 1.5 – 4.7), proton‐pump inhibitors (OR 2.1, 95% CI 1.3 – 3.4), and exposure to third (OR 2.4, 95% CI 1.4 – 4.2) or fourth generation (OR 2.1, 95% CI 1.2 – 3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3 – 0.9). Ninety‐two episodes of CDI were diagnosed among 79 SOT recipients (7.3%) and exposure to PPIs (OR 2.4, 95% CI 1.1 – 5.4) and third generation cephalosporin therapy (OR 3.9, 95% CI 1.4 – 10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.
Clinical coordination between primary (PC) and secondary care (SC) is a challenge for health systems, and clinical coordination mechanisms (CCM) play an important role in the interface between care levels. It is therefore essential to understand the elements that may hinder their use. This study aims to analyze the level of use of CCM, the difficulties and factors associated with their use, and suggestions for improving clinical coordination. A cross-sectional online survey-based study using the questionnaire COORDENA-CAT was conducted with 3308 PC and SC doctors in the Catalan national health system. Descriptive bivariate analysis and logistic regression models were used. Shared Electronic Medical Records were the most frequently used CCM, especially by PC doctors, and the one that presented most difficulties in use, mostly related to technical problems. Some factors positively associated with frequent use of various CCM were: working full-time in integrated areas, or with local hospitals. Interactional and organizational factors contributed to a greater extent among SC doctors. Suggestions for improving clinical coordination were similar between care levels and related mainly to the improvement of CCM. In an era where management tools are shifting towards technology-based CCM, this study can help to design strategies to improve their effectiveness.
Current guidelines for the management of community-acquired pneumonia (CAP) in children recommend obtaining a blood culture for children with moderate to severe pneumonia; yet, there is no guidance to assess the severity of the disease. Thus, a blood culture is obtained for the majority of children admitted with CAP, regardless of the severity of their symptoms. The study was designed to investigate and identify the prevalence of bacteremia in pediatric patients hospitalized with CAP and to evaluate the clinical and laboratory variables associated with bacteremia. We conducted a medical record review of children aged from two months to 18 years diagnosed with CAP between January 1, 2013, and December 31, 2017, at our two urban tertiary centers. We used binary logistic regression analysis and chi-square tests to look at factors associated with blood culture positivity. A total of 464 patients were admitted with CAP. Blood cultures were obtained in 357 (76.9%) patients; 23 patients had repeated cultures. Fifteen patients had positive cultures: 5/380 (1.3%) were considered true positive results and 10/380 (2.6%) were considered contaminants. Intensive care unit (ICU) admission (OR 5.6 with 95% CI (1- 31), p<0.03), toxic appearance (OR 12.8 with 95% CI (1.3-125), p300 mg/L (p<0.01) were associated with bacteremia. The prevalence of bacteremia among children admitted for CAP is low. The use of routine blood cultures should be reserved for children with moderate to severe pneumonia. Further studies are required to better risk-stratify children with CAP.
Background: Solid organ transplant (SOT) recipients are at increased risk for severe respiratory syncytial virus (RSV) disease due to chronic immunosuppression. Methods: In this ongoing, open-label, phase 3 trial, adults ≥18 years with a history of liver, kidney, or lung transplant received 2 doses of mRNA-1345 RSV vaccine (50 µg) 56 days apart. Primary endpoints were tolerability, safety, and RSV-A/RSV-B neutralizing antibody (nAb) responses on Day 85; secondary endpoints included immunogenicity on Days 29 and 181. Cell-mediated immunity was an exploratory endpoint assessed in a subset of participants. Results: 146/150 participants (median: age, 57 years; time since transplant, 4.7 years) received both doses. Reactogenicity was mild to moderate and transient. No vaccine-related discontinuations, deaths, adverse events of special interest (AESIs), or events of transplant rejection were reported within 28 days after any dose. One dose was immunogenic across all SOT types, with 4.9- and 3.4-fold increases in RSV-A/RSV-B nAb GMTs by Day 29, respectively. A second dose resulted in modest additional increases over baseline (RSV-A, 7.1-fold; RSV-B, 5.2-fold). Added benefit of the second dose was more apparent in participants with kidney and lung transplant, <2 years post-transplant, and on mycophenolate. Responses remained above baseline through Day 181. Polyfunctional CD4⁺ T-cell responses were robust and sustained; CD8⁺ responses were also observed. Conclusions: mRNA-1345 was well tolerated and immunogenic in SOT recipients. A single dose induced nAb responses across subgroups, with potential additional benefit from a second dose in specific groups. Durable antibody and cellular responses support mRNA-1345 as a preventive strategy for RSV in this vulnerable population. Clinical Trials Registration: NCT06067230.