IgG4 antibodies to the recombinant filarial antigen Wb-Bhp-1 decrease dramatically following treatment of lymphatic filariasis.
IgG4 antibodies to the recombinant filarial antigen Wb-Bhp-1 decrease dramatically following treatment of lymphatic filariasis.
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DOI：
10.1371/journal.pntd.0011364
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发表时间：
2023-06
影响因子：
3.8
通讯作者：
Weil, Gary J.
中科院分区：
文献类型：
--
作者：
Greene, Sarah E.;Huang, Yuefang;Curtis, Kurt C.;King, Christopher L.;Fischer, Peter U.;Weil, Gary J.
淋巴丝虫病（LF）是一种被忽视的热带疾病，也是导致慢性残疾的主要原因。由于在清除微丝虫血症的治疗后抗丝虫抗体或循环丝虫抗原血症长期持续存在，因此需要改进诊断测试。在这里，我们评估了抗丝虫治疗后重组丝虫抗原 Wb-Bhp-1、Wb123 和 Bm14 的抗体水平的变化。通过 ELISA 评估重组丝虫抗原的 IgG4 抗体。我们测试了来自巴布亚新几内亚临床试验的系列血浆样本。治疗前，90%、71% 和 99% 的参与者分别具有 Wb-Bhp-1、Wb123 和 Bm14 抗体。治疗 24 个月后，患有持续性微丝丝血症的参与者的 Wb-Bhp-1 和 Wb123 抗体（而非 Bm14）显着较高。尽管 76% 的参与者体内存在循环丝虫抗原，但在使用伊维菌素、二乙基卡马嗪和阿苯达唑治疗 60 个月后，所有三种抗原的抗体均显着下降。随访 60 个月时，分别有 17%、7% 和 90% 的参与者检测到 Wb-Bhp-1、Wb123 和 Bm14 抗体。在斯里兰卡进行的一项临床试验样本中，治疗后 Wb-Bhp-1 抗体的下降速度也比 Bm14 抗体下降得更快。我们还测试了生活在埃及丝虫病流行社区中具有不同感染特征的人们的存档血清样本。在 73% 的微丝蚴血症人群、53% 有循环丝虫抗原的无微丝蚴血症人群和 17.5% 无微丝蚴或循环丝虫抗原的地方病个体中检测到 Wb-Bhp-1 抗体。对来自印度的遗留样本进行的测试表明，很少有丝虫性淋巴水肿患者具有针对这些重组抗原的抗体。与循环丝虫抗原血症或 Bm14 抗体相比，Wb-Bhp-1 和 Wb123 抗体与持续性微丝虫血症的相关性更密切，并且在抗丝虫治疗后清除得更快。需要进行更多研究来评估 Wb-Bhp-1 血清学作为确定 LF 消除工作是否成功的工具的价值。淋巴丝虫病（LF）是世界卫生组织旨在消除的一种被忽视的热带疾病。公共卫生计划旨在通过在丝虫感染地区反复大规模分发抗丝虫药物来消除感染。这些大规模的药物管理活动非常成功。需要改进诊断测试来监测和验证感染消除工作是否成功。我们之前已经证明，检测重组寄生虫蛋白 Wb-Bhp-1 的抗体对于诊断活动性丝虫感染具有敏感性和特异性。在这里，我们发现 Wb-Bhp-1 抗体与治疗后血液中丝虫寄生虫的持续存在相关，并且在有效的抗丝虫治疗后它们会减少。重要的是，治疗后 Wb-Bhp-1 抗体比其他诊断标志物（例如循环丝虫抗原血症或 Bm14 抗体）下降得更快。因此，这种抗体测试可用作监测丝虫病消除计划是否成功的工具。
Lymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment. IgG4 antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to Wb-Bhp-1 and Wb123, but not Bm14, were significantly higher in participants with persistent microfilaremia 24 months after treatment. Antibodies to all three antigens declined significantly by 60 months after treatment with ivermectin, diethylcarbamazine and albendazole despite circulating filarial antigen in 76% of participants. By 60 months follow up, antibodies to Wb-Bhp-1, Wb123, and Bm14 were detected in 17%, 7% and 90% of participants, respectively. Antibodies to Wb-Bhp-1 also declined more rapidly after treatment than antibodies to Bm14 in samples from a clinical trial conducted in Sri Lanka. We also tested archived serum samples from people living in filariasis-endemic communities in Egypt with different infection profiles. Antibodies to Wb-Bhp-1 were detected in 73% of microfilaremic people, 53% of amicrofilaremic people with circulating filarial antigen, and 17.5% of endemic individuals without microfilaria or circulating filarial antigen. Tests performed with legacy samples from India showed that few people with filarial lymphedema had antibodies to these recombinant antigens. Antibodies to Wb-Bhp-1 and Wb123 are more closely correlated with persistent microfilaremia than circulating filarial antigenemia or antibodies to Bm14, and they clear more rapidly after anti-filarial treatment. Additional studies are needed to assess the value of Wb-Bhp-1 serology as a tool for determining the success of LF elimination efforts. Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination by the World Health Organization. Public health programs aim to eliminate the infection with repeated rounds of mass distribution of anti-filarial medicines in areas with LF. These mass drug administration campaigns have been highly successful. Improved diagnostic tests are needed to monitor and verify the success of infection elimination efforts. We have previously shown that detection of antibodies to the recombinant parasite protein Wb-Bhp-1 are sensitive and specific for diagnosis of active filarial infections. Here, we show that antibodies to Wb-Bhp-1 are correlated with the persistence of filarial parasites in the blood after treatment, and that they decrease after effective anti-filarial treatment. Importantly, antibodies to Wb-Bhp-1 decrease after treatment more rapidly than other diagnostic markers such as circulating filarial antigenemia or antibodies to Bm14. Thus, this antibody test may be useful as a tool for monitoring the success of filariasis elimination programs.
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DOI：
10.1056/nejmoa1706854
发表时间：
2018-11-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
King CL;Suamani J;Sanuku N;Cheng YC;Satofan S;Mancuso B;Goss CW;Robinson LJ;Siba PM;Weil GJ;Kazura JW
通讯作者：
Kazura JW
影响因子：
4.4
作者：
Li BW;Wang Z;Rush AC;Mitreva M;Weil GJ
通讯作者：
Weil GJ
DOI：
10.4269/ajtmh.1970.19.181
发表时间：
1970-01-01
影响因子：
3.3
作者：
BEAVER, PC
通讯作者：
BEAVER, PC
影响因子：
2.6
作者：
Goel, Ravishankar S.;Verma, Nimesh S.;Ashdown, Andrew C.
通讯作者：
Ashdown, Andrew C.
影响因子：
2
作者：
Krushna, N. S. A.;Shiny, C.;Narayanan, R. B.
通讯作者：
Narayanan, R. B.