Kabir K M Ahsanul, Sigera Chathurani, Maduranga Sachith, Weeratunga Praveen, Rajapakse Senaka, Fernando Deepika, Lloyd Andrew R, Bull Rowena A, Rodrigo Chaturaka
Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
PLoS One. 2025 Jul 7;20(7):e0326995. doi: 10.1371/journal.pone.0326995. eCollection 2025.
Dengue is a significant threat to human health in South and Southeast Asia where patients are treated without diagnostic confirmation during outbreaks. This approach, though cost-effective may miss important infections especially those caused by other arboviruses (e.g., Zika, Chikungunya and West Nile virus). This study aimed to diagnose missed infections mimicking dengue by using metagenomic next generation sequencing (mNGS).
Total nucleic acid (DNA and RNA) was extracted and subjected to mNGS from acute infection plasma of 60 patients from a prospective cohort study in Sri Lanka in which patients with clinically suspected dengue fever were recruited but were later confirmed as dengue-negative by NS1 antigen testing and by dengue-specific reverse transcription and polymerase chain reaction (RT-PCR) analysis. mNGS data revealed missed chikungunya and dengue infections in five patients each, and a possible bacterial infection by Klebsiella pneumoniae in another patient. It was not possible to differentiate chikungunya infections from dengue infections based on clinical features or routine non-diagnostic laboratory tests conducted in early infection (e.g., full blood count, C-reactive protein level). Phylogenetic analysis showed that the chikungunya sequences from this study were closely related to those sequenced from Maldives, Malaysia, India and Singapore between 2015-2019.
Chikungunya infection may masquerade as dengue especially in low- and middle-income countries where dengue is treated based on clinical suspicion only - without confirmatory testing. As both infections are likely prevalent worldwide, but the complications and natural history of chikungunya and dengue infections are quite different, the addition of cheap and accessible diagnostics for both infections should be pursued in endemic countries.
登革热对南亚和东南亚地区的人类健康构成重大威胁，在这些地区，疫情爆发期间患者在未经诊断确认的情况下就接受治疗。这种方法虽然具有成本效益，但可能会遗漏重要感染，尤其是由其他虫媒病毒（如寨卡病毒、基孔肯雅病毒和西尼罗河病毒）引起的感染。本研究旨在通过宏基因组下一代测序（mNGS）诊断疑似登革热的漏诊感染。
从斯里兰卡一项前瞻性队列研究的60例患者的急性感染血浆中提取总核酸（DNA和RNA），并进行mNGS检测。该队列研究招募了临床疑似登革热发热的患者，但后来通过NS1抗原检测以及登革热特异性逆转录和聚合酶链反应（RT-PCR）分析确认为登革热阴性。mNGS数据显示，分别有5例患者漏诊了基孔肯雅病毒和登革热感染，另有1例患者可能感染了肺炎克雷伯菌。根据临床特征或早期感染时进行的常规非诊断性实验室检查（如全血细胞计数、C反应蛋白水平），无法区分基孔肯雅病毒感染和登革热感染。系统发育分析表明，本研究中的基孔肯雅病毒序列与2015 - 2019年间从马尔代夫、马来西亚、印度和新加坡测序的序列密切相关。
基孔肯雅病毒感染可能会伪装成登革热，尤其是在中低收入国家，这些国家仅根据临床怀疑治疗登革热，而不进行确诊检测。由于这两种感染在全球可能都很普遍，但基孔肯雅病毒和登革热感染的并发症和自然史有很大不同，流行国家应增加针对这两种感染的廉价且可及的诊断方法。
