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Abstract Background In Ethiopia, neonatal mortality accounts for approximately 54% of under-five deaths with the majority of these deaths driven by infections. Possible Severe Bacterial Infection (PSBI) in neonates is a syndromic diagnosis that non-clinical health care providers use to identify and treat newborns with signs of sepsis. In low- and middle–income countries, referral to a hospital may not be feasible due to transportation, distance or finances. Growing evidence suggests health extension workers (HEWs) can identify and manage PSBI at the community level when referral to a hospital is not possible. However, community-based PSBI care strategies have not been widely scaled-up. This study aims to understand general determinants of household-level care as well as household care seeking and decision-making strategies for neonatal PSBI symptoms. Methods We conducted eleven focus group discussions (FGDs) to explore illness recognition and care seeking intentions from four rural kebeles in Amhara, Ethiopia. FGDs were conducted among mothers, fathers and households with recruitment stratified among households that have had a newborn with at least one symptom of PSBI (Symptomatic Group), and households that have had a newborn regardless of the child’s health status (Community Group). Data were thematically analyzed using MAXQDA software. Results Mothers were described as primary caretakers of the newborn and were often appreciated for making decisions for treatment, even when the father was not present. Type of care accessed was often dependent on conceptualization of the illness as simple or complex. When symptoms were not relieved with clinical care, or treatments at facilities were perceived as ineffective, alternative methods were sought. Most participants identified the health center as a reliable facility. While designed to be the first point of access for primary care, health posts were not mentioned as locations where families seek clinical treatment. Conclusions This study describes socio-contextual drivers for PSBI treatment at the community level. Future programming should consider the role community members have in planning interventions to increase demand for neonatal care at primary facilities. Encouragement of health post utilization could further allow for heightened accessibility-acceptability of a simplified PSBI regimen.

Abstract Background Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods A prospective, case–control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7–7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p

Background: Severe bacterial infections (SBIs) in otherwise healthy children are rare and may represent an underlying impairment of the immune system, including primary immunodeficiency. However, it is unclear whether and how children should be assessed., Methods: We retrospectively analyzed data from hospital records of previously healthy children aged 3 days to 18 years with SBI, including pleuropneumonia, meningitis, and/or sepsis. Patients were diagnosed or immunologically followed up between 1 January 2013 and 31 March 2020., Results: Among 432 children with SBI, findings could be analyzed in 360. Follow-up data were available for 265 children (74%), of whom 244 (92%) underwent immunological testing. Laboratory abnormalities were found in 51 of 244 patients (21%), with 3 deaths (1%). Fourteen children (6%) had immunodeficiency considered clinically relevant (3 complement deficiencies, 1 autoimmune neutropenia, 10 humoral immunodeficiencies), and 27 (11%) had milder humoral abnormalities or findings suggestive of delayed adaptive immune maturation., Conclusions: A substantial proportion of children with SBI may benefit from routine immunological testing, revealing (potentially) clinically relevant impaired immune function in 6%-17% of children. The identification of immune abnormalities allows for specific counseling of families and optimization of preventive measures, such as booster vaccinations, to avoid future SBI episodes., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aim: To assess the performance of a new clinical decision rule (CDR) to identify patients at a low risk of invasive bacterial infection (IBI) among febrile children and its theoretical impact on antibiotic use., Methods: Prospective study including consecutive children <5 years of age who presented in one French paediatric emergency department with fever without source between January and December 2016. With the collected data, we constructed a CDR based on a sequential approach based on age, clinical toxic signs, urinalysis and procalcitonin level. We evaluated its diagnostic performances to identify IBI and its potential impact on antibiotic use., Results: Among the 1061 children (IBI 11/1061, 1.0%), 693 (65.3%) were classified at low or intermediate risk of IBI, with an IBI prevalence of 0%. The sensitivity and specificity of the CDR to predict IBI were 100% and 73.9%. Negative and positive predictive value were 100% and 3.9%, respectively. Using this new CDR, the current antibiotics exposure would theoretically be reduced from 33.6% to 24.1%., Conclusion: The promising interest of this clinical decision rule, using simple and accessible biological and clinical tools, needs to be confirm with an external validation study, which will allow its use in clinical practice., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: The pharmacokinetic/pharmacodynamic (PK/PD) index of carbapenems that best correlates with in vivo antimicrobial activity is percent time of dosing interval in which free drug concentration remains above MIC (%fT > MIC), while the magnitudes of the PK/PD index of carbapenems remains undefined in critically ill sepsis patients. Methods: A sepsis rat model was first developed by comparing the survival outcomes after intraperitoneal injection of different inoculum size (1–10 × 107 CFU) of Pseudomonas aeruginosa ATCC9027 (MIC = 0.125 mg/L) in neutropenic rats. The PK characteristics of the model drug meropenem in the developed sepsis rat model was then evaluated, and PK modeling and simulation was applied to design meropenem dosing regimens attaining various PD targets (40%fT > MIC, 100%fT > MIC, and 100%fT > 4 × MIC). The microbiological response and survival outcomes for different meropenem treatment regimens were investigated in the rat sepsis model (n = 12 for each group). Results: The optimal inoculum for the rat sepsis model was 1 × 107 CFU of Pseudomonas aeruginosa ATCC9027. A one-compartment model with first-order absorption best described the PK of meropenem in sepsis rats. Pronounced survival prolongation and lower hazard risk were observed in the treatment groups of 50 or 75 mg/kg/q2.4h (100%fT > MIC) and 75 mg/kg/q2h (100%fT > 4 × MIC) compared to the 75 mg/kg/q6h (40%fT > MIC) group, while meropenem groups with PD targets of 100%fT > MIC and 100%fT > 4 × MIC showed comparable survival curves. Microbiological response for different PD targets is inconclusive due to irregular bacterial counts in blood samples. Conclusions: The PD target of 40%fT > MIC is suboptimal for sepsis rats, and the aggressive 100%fT > 4 × MIC target does not provide a survival benefit against the target of 100%fT > MIC.

Objective: Fever continues to be the most frequent cause of care in the pediatric population. The uses of invasive and unnecessary tests result in discomfort to the patients. Local epidemiological data could help to refine screening strategies, especially in low resources settings. The present study aims to describe the prevalence of serious bacterial infections in infants with fever without source and to evaluate the usefulness of clinical and laboratory parameters in the identification of serious bacterial infections., Materials and Methods: We included all children aged 0-36 months presenting with fever without source between January 2015 and December 2017. Demographic and clinical characteristics, investigations, and management procedures were recorded at the time of inclusion. Potential predictors of serious bacterial infections were compared between patients with and without serious bacterial infections., Results: In total, 137 patients were included. Serious bacterial infections were diagnosed in 41 patients (29.9%; 95% CI, 22%-38%). The most frequent diagnosis in serious bacterial infection patients was urinary tract infection (78%). Serum C-reactive protein levels greater than 80 mg/L (odds ratio, 2.79 [1.14,6.86]) and total days with fever (odds ratio, 2.56 [1.81,3.62]) showed a significant association to predict serious bacterial infections., Conclusion: Most infants with fever without source presented self-limited febrile syndromes without evidence of severe bacterial infection. C-reactive protein levels greater than 80 mg/L and the number of previous days with fever were variables associated with the presence of serious bacterial infections. Our results need to be validated in other tropical countries.

BACKGROUND Severe bacterial infections initiate inadequate inflammation that leads to disseminated intravascular coagulation and death. OBJECTIVES To evaluate the influence of bacterial infection on blood viscosity and red blood cells (RBCs) morphology, and the ability of Calotropis procera proteins (CpLP) to prevent the patho-hemorheology in infected animals. METHODS Rheology of blood, atomic force microscopy measurements on specific blood elements and blood count were performed to examine changes in blood viscosity, RBCs morphology, platelets activation, and RBCs indices. FINDINGS Infected mice hold their blood rheological behaviour as compared to that of the control group. However, they presented hyperactivated platelets, RBCs at different stages of eryptosis, and variation on RBCs indices. CpLP administration in healthy animals altered blood behaviour from pseudoplastic to Bingham-like fluid. Such effect disappeared over time and by inhibiting its proteases. No alterations were observed in RBCs morphology or platelets. Treatment of infected animals with CpLP prevented the changes in RBCs indices and morphology. MAIN CONCLUSIONS The inflammatory process triggered by bacterial infection induced pathological changes in RBCs and platelets activation. Treatment of infected animals with CpLP prevented the emergence of RBCs abnormal morphology and this may have implications in the protective effect of CpLP, avoiding animal death.