BACKGROUND Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. METHODOLOGY/PRINCIPAL FINDINGS We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case). CONCLUSIONS/SIGNIFICANCE Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential.

中文翻译：

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在越南北部的一家国家三级医院，对住院的未确诊发烧的斑疹伤寒的诊断面临的挑战。

背景技术斑疹伤寒（ST）是东南亚非疟疾高热病的主要原因，但由于难以进行临床诊断和缺乏足够的诊断测试，其真正疾病负担的证据有限。为了描述ST的流行病学和临床特征，我们在越南河内的一家国立三级医院中使用多种诊断方法进行了一项观察性研究。方法/主要发现我们纳入了2012年6月至2013年5月之间有热病住院的1127例患者。通过PCR和/或ELISA筛查免疫球蛋白M（IgM）确诊，总共33例（2.9％）患者被确诊为ST：14间接免疫过氧化物酶测定（IIP）证实（42.4％），IIP和PCR证实19（57.6％）。以农业为生，结膜注射，焦char，天冬氨酸转氨酶升高和丙氨酸转氨酶升高与ST病例显着相关（校正比值比（aOR）：分别为2.8、3.07、48.8、3.51和4.13），合并症和中性粒细胞减少在ST病例中明显较少（ aOR：分别为0.29和0.27）。大多数ST病例未临床诊断为立克次体病（72.7％）。在15例ST病例中发现了针对单一抗原的显着IIP反应，而在11例ST病例中发现了对多种抗原的明显高反应。最常见的显性IIP反应是针对Karp抗原（8例），其次是Gilliam（4例）。IgM ELISA在急性样品中的最高诊断准确性为78％。在56 kDa型特异性抗原基因的系统发育分析中，多数（14例）位于与Karp有关的分支，其次是与Gilliam有关（两例），与Kato有关的（两例）和与TA763有关的分支（一例）。结论/意义在三级医院中，ST的临床和实验室诊断仍然具有挑战性。涵盖流行的O虫O. tsutsugamushi菌株的血清学和核酸扩增检测方法的实施是必不可少的。