San Francisco Foundation

Azithromycin mass drug administration (MDA) to ages 1-59 months can reduce childhood mortality; however, more evidence is needed to support targeting a narrower age range of 1-11 months. This trial assesses the efficacy of azithromycin MDA to 1-11-month-old children in reducing mortality in a real-world setting with integration of vitamin A delivery within the established Child Health Days platform in Burkina Faso. Mortalite Infantile Reduite par l'Administration de Masse de l'Azithromycine is a double-masked, cluster-randomised, placebo-controlled trial in Child Health Days communities in Burkina Faso. Primary healthcare centre catchment areas (Centres de Santé et de Promotion Sociale (CSPS)) were randomised 2:1 to deliver biannual azithromycin or placebo for 1-11-month-old children. Birth history data at the study endpoint were used to calculate mortality rates and compare between groups. From September 2021 to January 2024, 201 709 children in 303 CSPS received azithromycin and 100 959 children in 158 CSPS received placebo, with an overall treatment coverage of 85%. Mortality rates were 2.6 (95% CI 2.1 to 3.1) deaths per 1000 person-years in the azithromycin arm and 2.5 (95% CI 1.8 to 3.2) per 1000 person-years in the placebo arm. There was no significant difference in the mortality rates by arm (incidence rate ratio: 1.04; 95% CI 0.75 to 1.46; p value 0.80). There were 16 non-serious adverse events and no serious adverse events recorded during the trial. This trial demonstrates that azithromycin MDA for child survival can be scaled up and integrated into existing child health programmes but was unable to demonstrate an effect of azithromycin distribution on infant mortality. These findings indicate future policy decisions should consider treatment delivery to the larger age group of children up to 5 years old. The trial was funded by the Bill and Melinda Gates Foundation (INV-005395). NCT04716712.

Abstract Quantum error control and mitigation techniques help improve how quantum computers handle errors, making algorithms run more efficiently despite noisy hardware. These strategies work at the software level and are built into programs before they run on quantum machines. Unlike quantum error correction, which actively detects and fixes errors during computation, error mitigation does not use real-time corrections but instead reduces the impact of errors after computations. Error mitigation can also help reduce the extra resources needed for full error correction. This chapter explains how these techniques relate to each other, provides an overview of key error mitigation methods and their limitations, and highlights leading academic and technological players in this field. It also covers current trends, such as integrating error-aware programming, benchmarking performance, and ensuring access to quantum hardware for testing. To advance quantum computing, it is recommended that research ecosystems support specialized centers and contribute to key strategic areas in the field.

Abstract Legionella pneumophila (L.p.), an intracellular bacterial pathogen, hijacks the ubiquitin signaling network of its eukaryotic host cells to establish infection. Two families of L.p. secreted ubiquitin ligases are instrumental in the maturation of the Legionella-containing vacuole (LCV): the SidC/SdcA family, which catalyzes canonical ubiquitination, and the SidE family, which bypasses the E1-E2-E3 enzymatic cascade and directly conjugates ubiquitin to a target through a phosphoribosyl (PR) linkage. Here, we demonstrate that the coordinated activities of these two effector families generate a hyperstable, ubiquitin-rich structure surrounding the LCV. We propose a model in which an initial wave of SidC/SdcA-mediated canonical ubiquitination around the LCV is further modified by SidE family-driven PR-ubiquitination, resulting in a detergent-resistant “cloud”. The “cloud” is transient, breaking down as infection progresses, suggesting that L.p. reshapes the properties of the proteinaceous shell surrounding the vacuole to meet changing needs throughout its intracellular lifecycle. This unusual structure likely stabilizes and protects the LCV, shielding it from host defense mechanisms during early infection. Our findings reveal cellular consequences of effector interplay during infection and provide a foundation for future studies into the structure and function of the proteinaceous “cloud” surrounding the LCV.

Abstract Legionella pneumophila (L.p.), an intracellular bacterial pathogen, hijacks the ubiquitin signaling network of its eukaryotic host cells to establish infection. Two families of L.p. secreted ubiquitin ligases are instrumental in the maturation of the Legionella-containing vacuole (LCV): the SidC/SdcA family, which catalyzes canonical ubiquitination, and the SidE family, which bypasses the E1-E2-E3 enzymatic cascade and directly conjugates ubiquitin to a target through a phosphoribosyl (PR) linkage. Here, we demonstrate that the coordinated activities of these two effector families generate a hyperstable, ubiquitin-rich structure surrounding the LCV. We propose a model in which an initial wave of SidC/SdcA-mediated canonical ubiquitination around the LCV is further modified by SidE family-driven PR-ubiquitination, resulting in a detergent-resistant “cloud”. The “cloud” is transient, breaking down as infection progresses, suggesting that L.p. reshapes the properties of the proteinaceous shell surrounding the vacuole to meet changing needs throughout its intracellular lifecycle. This unusual structure likely stabilizes and protects the LCV, shielding it from host defense mechanisms during early infection. Our findings reveal cellular consequences of effector interplay during infection and provide a foundation for future studies into the structure and function of the proteinaceous “cloud” surrounding the LCV.

Trachoma mapping in Latin America is incomplete, especially in indigenous communities of the Amazon thought to be at highest risk. The aim of this study was to determine the prevalence of clinical, microbiological, and serologic evidence of trachoma in a remote area of the Peruvian Amazon. A population-based sample of households from rural communities in Alto Amazonas province was selected using two-stage cluster sampling. In children aged 1-9 years, conjunctival photographs, conjunctival swabs, and dried blood spots were collected. Photographs were graded for trachomatous inflammation-follicular (TF). Swabs were processed for Chlamydia trachomatis with a nucleic acid amplification test. Dried blood spots were assessed for antibody responses to C. trachomatis with a multiplex bead assay. A total of 778 children aged 1-9 years from 21 communities participated. The age-adjusted prevalence of TF among 1-9-year-old children was 25.4% (95%CI 21.3-29.5%), compared with 0.8% (95%CI 0.5-1.0%) for ocular C. trachomatis and 6.6% (95%CI 4.5-9.0%) for Pgp3-specific antibodies to C. trachomatis. This region of the Peruvian Amazon had a high burden of clinical trachoma but low levels of C. trachomatis ocular infection and seropositivity.

Soil floors are common in low-income countries and can harbor contamination from fecal waste. Soil/dust ingestion from floors or indirectly via hands, water and food can contribute to children's ingestion of fecal organisms. We assessed if finished (e.g., concrete) floors are associated with lower E. coli contamination in the domestic environment in rural Bangladesh. We collected samples from 1864 households over 3.5 years, including stored drinking water, child and caregiver hand rinses, courtyard soil, food, and flies (n=24,118 samples), and enumerated E. coli using IDEXX Quanti-Tray/2000. Controlling for socio-demographics, water/sanitation status, and animal ownership, households with finished floors had slightly lower log10-transformed E. coli counts (Δlog10=-0.10 (-0.20, 0.00)) and prevalence (prevalence ratio [PR]=0.90 (0.83, 0.98)) on child hands than households with soil floors; floor material was not associated with contamination levels in other sample types. In subgroup analyses, finished floors were associated with lower E. coli on child hands following heavy rainfall (Δlog10=-0.23 (-0.39, -0.07)), above-median temperature (Δlog10=-0.18 (-0.30, -0.06)), and in households with more domestic animals (Δlog10=-0.16 (-0.32, -0.01)). Finished floors were also associated with slightly lower contamination of stored water following heavy rainfall (PR=0.89 (0.81, 0.99)) and above-median temperature (PR=0.91 (0.84, 0.98)), and lower contamination of stored food following higher rainfall and temperature but the associations for food were not statistically significant. Measures to control enteric infections in low-income countries should test flooring improvements to reduce exposure to fecal contamination.

<h2>Abstract</h2><h3>Background</h3> We aim to characterize the spectrum of neuro-ophthalmic manifestations and their impact on visual acuity in a cohort of Ebola virus disease (EVD) survivors from the Western African outbreak from 2013 to 2016. <h3>Methods</h3> Patients, who previously underwent screening for enrollment in the Ebola Virus Persistence in Ocular Tissues and Fluids Study (EVICT study), were eligible for this post-hoc analysis. A review of collected data was performed, and neuro-ophthalmic manifestations including afferent pupillary defect, motility problems, and optic nerve diseases (optic pallor or atrophy) were analyzed. Statistical analysis was performed using Microsoft Excel (Microsoft Corporation, Redmond, WA); a p-value <0.05 was considered significant. <h3>Findings</h3> A total of 184 eyes of 115 patients were included in the analysis. The mean age was 32·2 ± 15·8 years, and the mean logMAR was 0·34 ± 0·68; Snellen visual acuity of 20/40. Of 184 eyes, twelve (6·5 %) eyes of 8 patients had optic nerve diseases, of which 4 had bilateral disease. The mean logMAR was significantly worse in patients with optic nerve disease (1·46 ± 1·21) than in those without (0·26 ± 0·55), p-value = 0·008. Ocular motility issues were identified in 11 of 115 patients (9·6 %), which included exotropia (n = 9), esotropia (n = 1), and vertical gaze palsy (n = 1). <h3>Interpretation</h3> In this post-hoc analysis, we identified a subset of EVD survivors with optic nerve diseases and motility disorders. Patients with optic nerve pathology showed worse visual acuity with severe vision impairment and rare association with neurologic symptoms.