Background

Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only.

Methods

Eligible infants were aged 0–59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology.

Findings

There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58–82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding.

Interpretation

Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions.

Funding

The Bill and Melinda Gates Foundation.

中文翻译：

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使用 WHO 定义对南亚新生儿疾病的传染性病因进行分类：ANISA 研究的初步分析

背景

在全球范围内，新生儿死亡率几乎占 5 岁以下儿童死亡总数的一半。新生儿感染的病原体很难识别，因为临床症状是非特异性的。使用来自南亚新生儿感染病因学 (ANISA) 队列的数据，我们旨在描述使用 2015 年 WHO 危重病、临床严重感染和呼吸急促的病例定义进行事后分类的急性新生儿疾病的传染性病因谱只要。

方法

符合条件的婴儿年龄在 0-59 天，可能患有严重的细菌感染，而健康婴儿则参加了孟加拉国、印度和巴基斯坦的 ANISA 研究。我们应用部分潜伏类贝叶斯模型来估计 PCR 可检测到的 27 种病原体、仅通过血培养检测到的病原体以及不归因于任何传染性病因的疾病的流行率。分析中包括至少有一份临床标本可用的婴儿。我们根据世卫组织对重症、临床严重感染和迟发性呼吸急促婴儿的病例定义评估了这些病因的患病率。对于临床严重的定义，我们比较了细菌和病毒病因的体征流行率。

发现

危重类934名婴儿（992次），临床重症感染类3769名（4000次），迟发性孤立性呼吸急促类738名（771次）。我们估计重症组婴儿因细菌感染患病的比例为32·7%，临床重症感染组为15·6%，迟发性孤立性呼吸急促组婴儿为8·8%。在这些类别中，58-82% 的婴儿未发现传染性病因。在 4000 次临床严重感染中，细菌与病毒归因的患者体温过低、仅在刺激时运动、抽搐和喂养不良的比例较高。

解释

尽管可以考虑对最严重的病例定义进行修订，但我们的模型结果通常支持修订后的 WHO 病例定义。临床标准没有明确区分有和没有感染性病因的小婴儿。我们的研究结果强调需要改进即时诊断，并进一步研究未确定病因的新生儿死亡和发作，以确保抗生素管理和有针对性的干预措施。

资金

比尔和梅琳达盖茨基金会。