Infectious Diseases Division, Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, United States of America.
Infectious Diseases Division, Washington University School of Medicine, St Louis, Missouri, United States of America.
PLoS Negl Trop Dis. 2022 May 23;16(5):e0010407. doi: 10.1371/journal.pntd.0010407. eCollection 2022 May.
Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment.
METHODOLOGY/PRINCIPAL FINDINGS: We identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a single exon that encodes a 16.3 kD protein (Wb-Bhp-1) with 45% amino acid identity to BmR1. Immunohistology shows that anti-Wb-Bhp-1 antibodies primarily bind to Mf. Plasma from 124 of 224 (55%) microfilaremic individuals had IgG4 antibodies to Wb-Bhp-1 by ELISA. Serologic reactivity to Wb-Bhp-1 varied widely with samples from different regions (sensitivity range 32-92%), with 77% sensitivity for 116 samples collected from microfilaremic individuals outside of sub-Saharan Africa. This variable sensitivity highlights the importance of validating new diagnostic tests for parasitic diseases with samples from different geographical regions. Individuals with higher Mf counts were more likely to have anti-Wb-Bhp-1 antibodies. Cross-reactivity was observed with a minority of plasma samples from people with onchocerciasis (17%) or loiasis (10%). We also identified, cloned and characterized BmR1 homologues from O. volvulus and L. loa that have 41% and 38% identity to BmR1, respectively. However, antibody assays with these antigens were not sensitive for onchocerciasis or loiasis.
Wb-Bhp-1 is a novel antigen that is useful for serologic diagnosis of bancroftian filariasis. Additional studies are needed to assess the value of this antigen for monitoring the success of filariasis elimination programs.
淋巴丝虫病（LF）是一种由班氏丝虫、马来丝虫和帝汶丝虫引起的被忽视的热带病。全球消除淋巴丝虫病规划采用抗丝虫药物的大规模药物治疗（MDA），以清除血液中的微丝蚴（Mf），从而阻断蚊子的传播。需要新的诊断工具来评估 MDA 对班氏丝虫病的影响，因为在成功治疗后，现有的血清学检测仍可能呈阳性。
方法/主要发现：我们鉴定了 Wb-bhp-1，它编码班氏丝虫的 BmR1 同源物，B. malayi 蛋白用于诊断布氏丝虫病的 Brugia Rapid 抗体检测。Wb-bhp-1 有一个单一的外显子，编码一个 16.3 kD 的蛋白（Wb-Bhp-1），与 BmR1 的氨基酸序列有 45%的同源性。免疫组织化学显示，抗-Wb-Bhp-1 抗体主要与 Mf 结合。通过 ELISA，224 名微丝蚴血症患者中有 124 名（55%）的血浆具有针对 Wb-Bhp-1 的 IgG4 抗体。血清学反应性因地区不同而有很大差异（敏感性范围为 32-92%），来自撒哈拉以南非洲以外微丝蚴血症患者的 116 份样本的敏感性为 77%。这种可变的敏感性突出表明，用来自不同地理区域的样本验证新的寄生虫病诊断测试的重要性。Mf 计数较高的个体更有可能产生抗-Wb-Bhp-1 抗体。与少数患有盘尾丝虫病（17%）或罗阿丝虫病（10%）的人的血浆样本发生交叉反应。我们还鉴定、克隆和表征了 O. volvulus 和 L. loa 的 BmR1 同源物，它们与 BmR1 的同源性分别为 41%和 38%。然而，这些抗原的抗体检测对盘尾丝虫病或罗阿丝虫病并不敏感。
Wb-Bhp-1 是一种新的抗原，可用于班氏丝虫病的血清学诊断。需要进一步研究来评估这种抗原在监测丝虫病消除规划成功方面的价值。
