Daily Sepsis Research Analysis

BACKGROUND: Children in resource-constrained settings (RCS) have disproportionately high illness and mortality; however, the prevalence in RCS of paediatric acute critical illness (P-ACI; life-threatening conditions that require time-sensitive interventions) is unknown. Most P-ACI can be managed with basic critical care (stabilisation, fluid resuscitation, oxygen, and vital-organ support), but RCS hospitals often lack such essential services. This study estimated the prevalence and examined the aetiology of P-ACI among children at RCS hospitals to support critical care capacity building and inform resource allocation. METHODS: We conducted a hybrid prospective cohort and multinational point prevalence study of acutely ill or injured children aged 28 days to 14 years who presented to RCS hospitals on four designated days between July 20, 2021, and July 12, 2022. We measured the proportion of participants with P-ACI, applying the definition for acute paediatric critical illness (DEFCRIT) framework for research in resource-variable settings, and followed up admitted patients for hospital outcomes. In participants with P-ACI, we report diagnoses associated with critical illness. We used descriptive statistics to summarise site and cohort data by country sociodemographic category (Socio-demographic Index; SDI) and multivariable logistic regression to assess whether country sociodemographic category was independently associated with P-ACI. FINDINGS: The study included 46 sites, 19 countries, and 7538 children, among whom 2651 (35·2%) were admitted to hospital and 68 died (all-cause mortality 0·9% [95% CI 0·7-1·1]). 985 (13·1% [95% CI 12·3-13·9]) participants had P-ACI. Among all sociodemographic categories, P-ACI prevalence was highest (28·0% [26·0-30·1]; 512 of 1828 participants) in low-SDI countries (p<0·0001). Mortality among those with P-ACI was 6·3% (4·9-8·0; 62 deaths). The most common P-ACI diagnoses were pneumonia (152 [15·4%] of 985 participants), sepsis or septic shock (102 [10·4%]), and malaria (95 [9·6%]). In an adjusted model, country sociodemographic category was not significantly associated with P-ACI frequency. Among all 68 deaths in the study, 40 (59% [46-71]) occurred within 48 h of presentation. INTERPRETATION: P-ACI in RCS hospitals is common, associated with high mortality, disproportionately elevated in low-SDI countries, and associated with conditions that can be managed with basic critical care. This study underlines the need for investment in basic critical care services in RCS to address a major contributor to preventable mortality in hospitalised children. FUNDING: National Institutes of Health (USA); Medical Research Council (Singapore); Grand Challenges Canada; and University of Maryland, Baltimore (USA). TRANSLATIONS: For the French, Portuguese and Spanish translations of the abstract see Supplementary Materials section.

BACKGROUND: Leptospirosis is a globally neglected re-emerging zoonosis affecting all mammals, albeit with variable outcomes. Humans are susceptible to leptospirosis; infection with Leptospira interrogans species can cause severe disease in humans, with multi-organ failure, mainly affecting kidney, lung and liver function, leading to death in 10% of cases. Mice and rats are more resistant to acute disease and can carry leptospires asymptomatically in the kidneys and act as reservoirs, shedding leptospires into the environment. The incidence of leptospirosis is higher in tropical countries, and countries with poor sanitation, where heavy rainfall and flooding favour infection. Diagnosis of leptospirosis is difficult because of the many different serovars and the variety of clinical symptoms that can be confused with viral infections. The physiopathology is poorly understood, and leptospirosis is often regarded as an inflammatory disease, like sepsis. METHODS: To investigate the causes of death in lethal leptospirosis, we compared intraperitoneal infection of male and female C57BL6/J mice with 10 FINDINGS: Neither lung, liver, pancreas or kidney damage nor massive necroptosis or cytokine storm could explain the lethality. Although we did not find pro-inflammatory cytokines, we did find elevated levels of the anti-inflammatory cytokine IL-10 and the chemokine RANTES in the serum and organs of Leptospira-infected mice. In contrast, severe leptospirosis was associated with neutrophilia and vascular permeability, unexpectedly due to neutrophils and not only due to Leptospira infection. Strikingly, the main cause of death was myocarditis, an overlooked complication of human leptospirosis. INTERPRETATION: Despite clinical similarities between bacterial sepsis and leptospirosis, striking differences were observed, in particular a lack of cytokine storm in acute leptospirosis. The fact that IL-10 was increased in infected mice may explain the lack of pro-inflammatory cytokines, emphasising the covert nature of Leptospira infections. Neutrophilia is a hallmark of human leptospirosis. Our findings confirm the ineffective control of infection by neutrophils and highlight their deleterious role in vascular permeability, previously only attributed to the ability of leptospires to damage and cross endothelial junctions. Finally, the identification of death due to myocarditis rather than kidney, liver or liver failure may reflect an overlooked but common symptom associated with poor prognosis in human leptospirosis. These features of neutrophilia and myocarditis are also seen in patients, making this mouse model a paradigm for better understanding human leptospirosis and designing new therapeutic strategies. FUNDING: The Boneca laboratory was supported by the following programmes: Investissement d'Avenir program, Laboratoire d'Excellence "Integrative Biology of Emerging Infectious Diseases" (ANR-10-LABX-62-IBEID) and by R&D grants from Danone and MEIJI. CW received an ICRAD/ANR grant (S-CR23012-ANR 22 ICRD 0004 01). SP received a scholarship by Université Paris Cité (formerly Université Paris V - Descartes) through Doctoral School BioSPC (ED562, BioSPC). SP has additionally received a scholarship "Fin de Thèse de Science" number FDT202404018322 granted by "Fondation pour la Recherche Médicale (FRM)". The funders had no implication in the design, analysis and reporting of the study.

BACKGROUND: Fluid resuscitation is a cornerstone of septic shock management in pediatric patients, with normal saline (NS) being the traditional choice. However, balanced solutions (BS) have gained attention due to their potential to mitigate acid-base and electrolyte disturbances. Despite this, the optimal choice between BS and NS for pediatric sepsis remains unclear. Therefore, we aimed to conduct a meta-analysis comparing the clinical outcomes of BS versus NS in pediatric patients with sepsis. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, along with reference lists of retrieved publications, for studies comparing clinical outcomes in pediatric patients with sepsis treated with BS versus NS. Our outcomes of interest included acute kidney injury (AKI), hospital mortality, hospital length of stay, pediatric intensive care unit (PICU) length of stay, need for renal replacement therapy, hyperchloremia and mechanical ventilation. We performed statistical analysis using Review Manager Web 8.0.0 and Rstudio. RESULTS: We included 12,231 patients from 8 studies, of which 4 were randomized clinical trials (RCTs). BS was used to treat septic shock in 2,460 (20.1%) patients. The mean age was 5.98 ± 3.08 years, with 43.82% female patients. Follow-up ranged from 3 to 90 days. We found no statistically significant difference between groups in AKI, hospital mortality, mechanical ventilation, need for renal replacement therapy, and PICU length of stay. Hospital length of stay in days was significantly longer with BS compared to NS (MD 3.38; 95% CI 1.13 to 5.64; p = 0.003; I² = 0%) and the occurrence of hyperchloremia was lower in the BS compared to NS (RR 0.70; 95% CI 0.59 to 0.82; p = 0.0001; I² = 0%). In a subgroup analysis of RCTs only, AKI occurrence was not significantly different between BS and NS groups (RR 0.81; 95% CI 0.48 to 1.38; p = 0.44; I² = 18%). However, the need for renal replacement therapy was significantly less frequent in patients treated with BS compared to NS (RR 0.58; 95% CI 0.39 to 0.87; p = 0.008; I² = 0%). CONCLUSION: In pediatric septic shock patients, treatment with balanced solutions (BS) was associated with a lower need for renal replacement therapy and a reduced occurrence of hyperchloremia. However, hospital length of stay was longer in patients treated with BS compared to those receiving normal saline (NS). These results underscore the complexity of fluid management in pediatric septic shock and emphasize the need for further research.