Neurological manifestations of scrub typhus infection: A systematic review and meta-analysis of clinical features and case fatality.
Neurological manifestations of scrub typhus infection: A systematic review and meta-analysis of clinical features and case fatality.
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DOI：
10.1371/journal.pntd.0010952
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发表时间：
2022-11
影响因子：
3.8
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中科院分区：
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恙虫病已成为流行地区中枢神经系统（CNS）感染的主要原因。作为一种可治疗的疾病，及时发现是至关重要的。然而，很少有研究集中在描述神经恙虫病感染的症状和结果。我们进行了一项系统回顾和荟萃分析，报告了中枢神经系统恙虫病感染患者的临床特征和病死率（CFR）。搜索和分析计划发表在PROSPERO [ID 328732]。对PubMed和Scopus进行了系统检索，并纳入了描述经证实的恙虫病感染的中枢神经系统表现的患者的研究。研究的结果是加权疾病期间临床特征的合并患病率（WPP）和加权CFR。19项研究纳入1,221名患者（656名成人和565名儿科）。中枢神经系统恙虫病最常见的临床特征是符合非特异性急性脑炎综合征（AES），如发热（WPP 100.0% [99.5% ~ 100.0%, I2 = 47.8%]）、感觉改变（67.4% [54.9 ~ 78.8%,I2 = 93.3%]）、头痛（65.0% [51.5 ~ 77.6%,I2 = 95.1%]）和颈部僵硬56.6% （29.4 ~ 80.4%,I2 = 96.3%）。很少发现恙虫病的典型特征；结痂仅占20.8% (9.8% ~ 34.3%,I2 = 95.4%)，淋巴结病变占24.1% （95% CI 11.8% ~ 38.9%, I2 = 87.8%）。合并CFR （95% CI）为3.6% （1.5% - 6.4%,I2 = 67.3%）。儿科队列的CFR为6.1% (1.9-12.1%,I2 = 77%)，而成人队列为2.6% （0.7-5.3%,I2 = 43%）。我们的荟萃分析表明，有恙虫病中枢神经系统表现的患者中有3.6%死亡。在流行地区，临床医生应高度怀疑出现AES的恙虫病患者，并考虑在等待调查结果的同时开始经验性治疗，即使没有典型体征，如疮痂或淋巴结病。恙虫病是流行地区急性脑炎综合征的主要病因，但其临床特征和病死率尚未得到充分描述。我们进行了系统回顾和荟萃分析，发现患有神经性恙虫病的成人通常表现为头痛和颈部僵硬，而儿童则表现为感觉改变和癫痫发作活动。典型的与恙虫病相关的体征，如疮痂和淋巴结病，通常没有报道。有恙虫病神经系统症状的患者中只有不到4%在医院死亡，儿童的病死率可能更高。当患者在流行地区出现神经系统感染时，临床医生应该有较低的门槛开始对恙虫病进行经验性治疗。
Scrub typhus has become a leading cause of central nervous system (CNS) infection in endemic regions. As a treatable condition, prompt recognition is vital. However, few studies have focused on describing the symptomology and outcomes of neurological scrub typhus infection. We conducted a systematic review and meta-analysis to report the clinical features and case fatality ratio (CFR) in patients with CNS scrub typhus infection. A search and analysis plan was published in PROSPERO [ID 328732]. A systematic search of PubMed and Scopus was performed and studies describing patients with CNS manifestations of proven scrub typhus infection were included. The outcomes studied were weighted pooled prevalence (WPP) of clinical features during illness and weighted CFR. Nineteen studies with 1,221 (656 adults and 565 paediatric) patients were included. The most common clinical features in CNS scrub typhus were those consistent with non-specific acute encephalitis syndromes (AES), such as fever (WPP 100.0% [99.5%-100.0%, I2 = 47.8%]), altered sensorium (67.4% [54.9–78.8%, I2 = 93.3%]), headache (65.0% [51.5–77.6%, I2 = 95.1%]) and neck stiffness 56.6% (29.4–80.4%, I2 = 96.3%). Classical features of scrub typhus were infrequently identified; an eschar was found in only 20.8% (9.8%-34.3%, I2 = 95.4%) and lymphadenopathy in 24.1% (95% CI 11.8% - 38.9%, I2 = 87.8%). The pooled CFR (95% CI) was 3.6% (1.5%– 6.4%, I2 = 67.3%). Paediatric cohorts had a CFR of 6.1% (1.9–12.1%, I2 = 77%) whilst adult cohorts reported 2.6% (0.7–5.3%, I2 = 43%). Our meta-analyses illustrate that 3.6% of patients with CNS manifestations of scrub typhus die. Clinicians should have a high index of suspicion for scrub typhus in patients presenting with AES in endemic regions and consider starting empiric treatment whilst awaiting results of investigations, even in the absence of classical signs such as an eschar or lymphadenopathy. Scrub typhus is a leading cause of acute encephalitis syndrome in endemic regions, but its clinical features and case fatality rate are not yet fully described. We conducted a systemic review and meta-analysis and found that adults with neurological scrub typhus commonly present with headache and neck stiffness, whilst children present with altered sensorium and seizure activity. Signs classically associated with scrub typhus such as eschar and lymphadenopathy were not commonly reported. Just under 4% of patients with neurological manifestations of scrub typhus die in hospital, and the case fatality rate may be higher in children. Clinicians should have a low threshold to start empiric treatment for scrub typhus when patients present with neurological infections in endemic regions.
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