Circulating cell-free Nucleic Acid Detection for W. bancrofti infections

Marisa Salazar, Paul Schaughency, Thomas B Nutman, Sasisekhar Bennuru
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Abstract

Human lymphatic filariasis (LF) is primarily caused by helminth parasites Wuchereria bancrofti (Wb) and Brugia malayi (Bm). Detecting parasitic circulating cell free nucleic acids (ccfDNA/ccfRNA) in plasma is a promising approach for detection of active infections. Plasma-RNAseq analyses from individuals with active Wb infection and uninfected controls identified 6 RNA targets that were specific to Wb and/or Bm. Assays developed to detect either ccfDNA and ccfRNA were successfully used in Wb-infected individuals, but DNA-based assays targeting WbTR1 was found to be the most sensitive biomarker of Wb circulating cell free nucleic acids. Plasma-derived ccfDNA was identified in 71 % (of all mf-positive individuals) Wb infection from India, Cook Islands, Mali, Haiti and Guyana. Following definitive treatment, time course analyses indicated that WbTR1 ccfDNA levels were undetectable within a year. Overall, ccfDNA/RNA detection in LF holds promise for assessment of infection and treatment response in Wb and Bm infections.
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班氏梭菌感染的循环无细胞核酸检测
人淋巴丝虫病(LF)主要由班氏乌氏丝虫病(Wb)和马来布鲁氏丝虫病(Bm)引起。检测血浆中游离寄生循环细胞核酸(ccfDNA/ccfRNA)是一种很有前途的检测活动性感染的方法。血浆rnaseq分析来自活动性Wb感染和未感染对照的个体,鉴定出6个特异性针对Wb和/或Bm的RNA靶标。用于检测ccfDNA和ccfRNA的检测方法已成功地用于感染Wb的个体,但以dna为基础的针对WbTR1的检测被发现是Wb循环游离核酸最敏感的生物标志物。在来自印度、库克群岛、马里、海地和圭亚那的71%(所有阳性个体)的Wb感染中鉴定出血浆来源的ccfDNA。在最终治疗后,时间过程分析表明,一年内无法检测到WbTR1 ccfDNA水平。总之,ccfDNA/RNA在LF中的检测有望评估Wb和Bm感染的感染和治疗反应。
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