Instituto Nacional de Parasitología "Dr Mario Fatala Chaben" ANLIS MALBRÁN, Ministerio de Salud, Buenos Aires, Argentina.
Bayer US LLC, Whippany, New Jersey, United States.
PLoS Negl Trop Dis. 2023 Jun 23;17(6):e0011440. doi: 10.1371/journal.pntd.0011440. eCollection 2023 Jun.
Measurement of the success of antitrypanosomal treatment for Chagas disease is difficult, particularly in the chronic phase of the disease, because anti-Trypanosoma cruzi antibodies persist in serum for prolonged periods. We studied the effects of nifurtimox administered by two different treatment regimens on the T. cruzi calcium-binding flagellar protein F29 in children diagnosed with Chagas disease measured using an enzyme-linked immunosorbent assay (ELISA) technique (ELISA F29).
In a phase 3, randomized, double-blind, parallel-group, historically controlled study (ClinicalTrials.gov NCT02625974), blood samples obtained from children diagnosed with Chagas disease and treated with nifurtimox for either 60 days or 30 days were analyzed using an ELISA with an F29 recombinant protein as the antigen, as well as conventional serological tests (recombinant ELISA and indirect hemagglutination assay). In an exploratory approach, serological response to nifurtimox treatment was evaluated for 4 years post-treatment. In both treatment groups, the number of patients with negative ELISA F29 values increased over the period of observation. The incidence rate of negative seroconversion using ELISA F29 was 22.94% (95% CI: 19.65%, 26.63%) in the 60-day treatment group and 21.64% (95% CI: 17.21%, 26.86%) in the 30-day treatment group. In the subpopulation of patients who tested seropositive for F29 before nifurtimox treatment, 88 patients (67.7%) in the 60-day regimen and 39 patients (59.1%) in the 30-day regimen were F29 seronegative at 4 years post-treatment. All patients who had a positive ELISA F29 test at baseline and seroconverted to negative measured by conventional serology reached seronegativity in ELISA F29 earlier than in conventional serology.
The results demonstrate a serological response to treatment with nifurtimox measured by the ELISA F29 test in children diagnosed with Chagas disease. The F29-based ELISA can be considered a potential early marker of response to antitrypanosomal therapy for Chagas disease.
ClinicalTrials.gov NCT02625974.
抗恰加斯病（Chagas disease）治疗效果的测量较为困难，尤其是在疾病的慢性期，因为抗克氏锥虫（Trypanosoma cruzi）抗体在血清中会持续存在很长时间。我们研究了两种不同的硝呋替莫（nifurtimox）治疗方案对采用酶联免疫吸附试验（ELISA）技术检测的确诊恰加斯病儿童的克氏锥虫钙结合鞭毛蛋白 F29 的影响（ELISA F29）。
在一项 3 期、随机、双盲、平行组、历史对照研究（ClinicalTrials.gov NCT02625974）中，对接受硝呋替莫治疗 60 天或 30 天的确诊恰加斯病儿童的血液样本进行了分析，所用方法是 ELISA，以 F29 重组蛋白作为抗原，同时还采用了常规血清学检测（重组 ELISA 和间接血凝试验）。采用探索性方法，对治疗后 4 年的硝呋替莫治疗血清学反应进行了评估。在两组治疗中，接受观察的期间内，ELISA F29 检测值阴性的患者数量均有所增加。60 天治疗组和 30 天治疗组的 ELISA F29 血清学阴转的发生率分别为 22.94%（95%CI：19.65%，26.63%）和 21.64%（95%CI：17.21%，26.86%）。在硝呋替莫治疗前 F29 检测呈血清阳性的患者亚群中，60 天疗程的 88 例患者（67.7%）和 30 天疗程的 39 例患者（59.1%）在治疗后 4 年时 F29 为阴性。所有基线时 ELISA F29 检测呈阳性且通过常规血清学检测发生血清学转换的患者，在 ELISA F29 中达到阴性的时间早于常规血清学检测。
结果表明，ELISA F29 检测可反映确诊恰加斯病儿童接受硝呋替莫治疗的血清学反应。F29 基于 ELISA 可被视为治疗恰加斯病的抗锥虫治疗早期反应的潜在标志物。
ClinicalTrials.gov NCT02625974。
