The Childhood Acute Illness & Nutrition (CHAIN) Network, Nairobi, Kenya.
KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.
Sci Rep. 2019 Apr 12;9(1):5981. doi: 10.1038/s41598-019-42436-y.
High mortality after discharge from hospital following acute illness has been observed among children with Severe Acute Malnutrition (SAM). However, mechanisms that may be amenable to intervention to reduce risk are unknown. We performed a nested case-control study among HIV-uninfected children aged 2-59 months treated for complicated SAM according to WHO recommendations at four Kenyan hospitals. Blood was drawn from 1778 children when clinically judged stable before discharge from hospital. Cases were children who died within 60 days. Controls were randomly selected children who survived for one year without readmission to hospital. Untargeted proteomics, total protein, cytokines and chemokines, and leptin were assayed in plasma and corresponding biological processes determined. Among 121 cases and 120 controls, increased levels of calprotectin, von Willebrand factor, angiotensinogen, IL8, IL15, IP10, TNFα, and decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were associated with mortality after adjusting for possible confounders. Acute phase responses, cellular responses to lipopolysaccharide, neutrophil responses to bacteria, and endothelial responses were enriched among cases. Among apparently clinically stable children with SAM, a sepsis-like profile is associated with subsequent death. This may be due to ongoing bacterial infection, translocated bacterial products or deranged immune response during nutritional recovery.
急性疾病出院后的高死亡率在患有严重急性营养不良（SAM）的儿童中已被观察到。然而，目前尚不清楚哪些机制可能适合进行干预以降低风险。我们在肯尼亚的四家医院，根据世界卫生组织（WHO）的建议，对 2-59 个月大的 HIV 阴性患有复杂 SAM 的儿童进行了一项嵌套病例对照研究。在临床判断稳定后，在出院前从 1778 名儿童中抽取血液。病例为 60 天内死亡的儿童。对照为随机选择的在一年中未因再次住院而死亡的儿童。在血浆中测定了非靶向蛋白质组学、总蛋白、细胞因子和趋化因子以及瘦素，并确定了相应的生物学过程。在 121 例病例和 120 例对照中，校正可能的混杂因素后，与死亡率相关的有钙卫蛋白、血管性血友病因子、血管紧张素原、IL8、IL15、IP10、TNFα水平升高，瘦素、肝素辅因子 2 和血清对氧磷酶水平降低。急性相反应、细胞对脂多糖的反应、中性粒细胞对细菌的反应和内皮细胞的反应在病例中富集。在 SAM 儿童中，看似临床稳定的儿童中存在类似于败血症的特征与随后的死亡相关。这可能是由于持续的细菌感染、移位的细菌产物或在营养恢复期间免疫反应失调。
