High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection.
High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection.
复制标题
抗恙虫病东方体的高初始IgG抗体水平与严重恙虫病感染的风险增加有关。
DOI：
10.1371/journal.pntd.0009283
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发表时间：
2021-03
影响因子：
3.8
通讯作者：
Schmidt WP
中科院分区：
文献类型：
--
作者：
Devamani CS;Prakash JAJ;Alexander N;Stone W;Gunasekaran K;Rose W;Schmidt WP
恙虫病是亚洲许多地区发热性疾病的主要病因。免疫力受到恙虫病东方体菌株多样性的限制。目前尚不清楚先前的感染是否可以防止严重感染或增加风险。我们研究了抗O.采用酶联免疫吸附试验（ELISA）对636例恙虫病患者进行恙虫病检测。ELISA光密度（OD）和严重感染的风险之间的关联使用泊松回归建模。OD分为低（<1.0）、中等（1.0 - 2.9）和高（≥3.0）。还将OD建模为连续变量（三次样条）。病例的中位年龄为41岁（范围0-85岁），其中37%患有严重感染。与低水平分类相比，中等水平分类中严重感染的年龄调整风险高1.5倍（95%CI 1.2，1.9），高水平分类中严重感染的年龄调整风险高1.3倍（95%CI 1.0，1.7）。这种影响在<40岁的病例中更强，与低类别相比，中等和高类别的风险增加了一倍。在发热发作7天内检测的病例中，当IgG OD更可能反映感染前水平时，效果更明显。诊断时IgG抗体水平中等和较高与严重恙虫病感染的风险较高相关。这些发现可能是由于严重感染引起IgG反应加速或先前的恙虫病感染增强了随后发作的严重程度。在某些病毒感染中，重复感染与比首次感染更高的严重疾病风险相关。明确的临床和流行病学证据表明，这种影响只存在于登革病毒感染中，但它也可能在非病毒感染中发挥作用。恙虫病是由东方菌属的细胞内细菌引起的，是亚洲许多地区发热性疾病的最常见原因之一。尽管它很常见，可能致命，但它仍然是一种被忽视和诊断不足的感染。由于东方虫种类（特别是O.恙虫病）的人可以在生活中经历多次感染。在这项对来自印度南部的636例恙虫病病例的研究中，我们发现初始IgG抗体水平升高，可能来自早期感染，与严重疾病密切相关。这种效果在年轻患者和抗体水平中度升高时尤其明显。这一发现可能是由于严重感染引起IgG反应加速，或如登革热，先前的恙虫病感染增加了随后严重发作的风险。
Scrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk. We studied IgG antibody levels against O. tsutsugamushi at presentation in 636 scrub typhus patients using enzyme-linked immunosorbent assays (ELISA). The association between ELISA optical density (OD) and risk of severe infection was modelled using Poisson regression. OD was categorised as low (<1.0), intermediate (1.0 to 2.9), and high (≥3.0). OD was also modelled as a continuous variable (cubic spline). Median age of cases was 41 years (range 0–85), with 37% having severe infection. Compared to the low category, the age-adjusted risk of severe infection was 1.5 times higher in the intermediate category (95%CI 1.2, 1.9), and 1.3 times higher in the high category (95%CI 1.0, 1.7). The effect was stronger in cases <40 years, doubling the risk in the intermediate and high categories compared to the low category. The effect was more pronounced in cases tested within 7 days of fever onset when IgG ODs are more likely to reflect pre-infection levels. Intermediate and high IgG antibody levels at the time of diagnosis are associated with a higher risk of severe scrub typhus infection. The findings may be explained by severe infection eliciting an accelerated IgG response or by previous scrub typhus infection enhancing the severity of subsequent episodes. In some viral infections, repeat infection is associated with a higher risk of severe disease than the first infection. Clear clinical and epidemiological evidence for this effect only exists for dengue virus infection, but it may also play a role in non-viral infections. Scrub typhus is caused by intracellular bacteria of the Orientia genus, and is among the most common causes of febrile illness in many parts of Asia. Despite being common and potentially fatal, it remains a neglected and under-diagnosed infection. Due to the great strain diversity of Orientia species (especially O. tsutsugamushi) people can experience multiple infections during life. In this study of 636 scrub typhus cases from South India, we found elevated initial IgG antibody levels, possibly from an earlier infection, to be strongly associated with severe disease. The effect was especially pronounced in younger patients and at moderately elevated antibody levels. The findings may be explained by severe infection eliciting an accelerated IgG response or, as in dengue fever, by previous scrub typhus infection enhancing the risk of severe subsequent episodes.