Campos Marliane B, Lima Luciana V R, Vasconcelos Dos Santos Thiago, Ramos Patrícia K, Gomes Claudia M C, Laurenti Márcia D, Corbett Carlos E P, Shaw Jeffrey J, Silveira Fernando T
Evandro Chagas Institute (Surveillance Secretary of Health and Environment, Ministry of Health), Ananindeua, Pará, Brazil.
Medical School of São Paulo University, São Paulo, São Paulo, Brazil.
Parasit Vectors. 2025 Aug 5;18(1):336. doi: 10.1186/s13071-025-06941-6.
BACKGROUND: American cutaneous leishmaniasis (ACL) is a protozoan parasitic disease caused by different Leishmania spp. from L. (Leishmania) and L. (Viannia) subgenera. In Brazil, seven Leishmania spp. act as ACL agents. Infection with L. (L.) amazonensis presents a wide clinical-immunopathological spectrum, ranging from localized cutaneous leishmaniasis (LCL), which usually responds well to antimony therapy, to borderline disseminated cutaneous leishmaniasis (BDCL), which may require twice as much LCL-antimony therapy to cure, and, finally, to anergic diffuse cutaneous leishmaniasis (ADCL), which is highly resistant to any chemotherapy. This clinical variability is driven by different degrees of T-cell immunosuppression, which negatively impact delayed-type hypersensitivity (DTH), as assessed by the Montenegro skin test (MST). METHODS: Given MST's role as a T-cell-mediated resistance marker, we used it for diagnosing and monitoring patients with LCL (n = 8) and BDCL (n = 3) due to L. (L.) amazonensis to assess T-cell immunosuppression in these patients. MST was assessed at diagnosis and after treatment, although one patient with LCL refused treatment. The study took place at the Evandro Chagas Institute (Pará, Brazil), with diagnosis confirmed through parasitological assays, MST using L. (V.) braziliensis antigen, indirect fluorescent antibody test (IFAT)-immunoglobulin (Ig)G serology, histopathology, and PCR. Phenotypic and genotypic analyses were used to identify the primary agent. RESULTS: MST was negative in all patients, both before and after successful treatment. Notably, one patient with LCL who declined treatment also showed no MST reactivity both before and after spontaneous healing. The absence of MST reactivity persisted for up to 1 year postcure in LCL and up to 2 years in BDCL, indicating a sustained lack of MST reactivity regardless of treatment outcome or spontaneous healing. CONCLUSIONS: The lack of MST reactivity pre- and post-treatment in LCL and BDCL challenges the role of DTH as a marker for T-cell-mediated resistance to L. (L.) amazonensis infection. Moreover, the first case of spontaneous LCL cure by L. (L.) amazonensis showed no MST reactivity pre- or post-resolution, raising doubts about the role of DTH in this process.
背景：美洲皮肤利什曼病（ACL）是一种由来自利什曼原虫属（Leishmania）和维扬尼利什曼原虫亚属（Viannia）不同利什曼原虫种引起的原生动物寄生虫病。在巴西，七种利什曼原虫种是ACL的病原体。感染亚马逊利什曼原虫（L. (L.) amazonensis）会呈现出广泛的临床免疫病理谱，从通常对抗锑疗法反应良好的局限性皮肤利什曼病（LCL），到可能需要两倍于LCL抗锑疗法剂量才能治愈的边缘性播散性皮肤利什曼病（BDCL），最后到对任何化疗都具有高度抗性的无反应性弥漫性皮肤利什曼病（ADCL）。这种临床变异性是由不同程度的T细胞免疫抑制驱动的，通过蒙氏皮肤试验（MST）评估，这种免疫抑制会对迟发型超敏反应（DTH）产生负面影响。 方法：鉴于MST作为T细胞介导抗性标志物的作用，我们将其用于诊断和监测因亚马逊利什曼原虫（L. (L.) amazonensis）感染导致的LCL（n = 8）和BDCL（n = 3）患者，以评估这些患者的T细胞免疫抑制情况。在诊断时和治疗后评估MST，尽管有一名LCL患者拒绝治疗。该研究在埃万德罗·查加斯研究所（巴西帕拉州）进行，通过寄生虫学检测、使用巴西利什曼原虫（L. (V.) braziliensis）抗原的MST、间接荧光抗体试验（IFAT）-免疫球蛋白（Ig）G血清学、组织病理学和PCR来确诊。采用表型和基因型分析来鉴定主要病原体。 结果：在所有患者中，治疗成功前后MST均为阴性。值得注意的是，一名拒绝治疗的LCL患者在自发愈合前后也未表现出MST反应性。LCL患者治愈后MST无反应性持续长达1年，BDCL患者则长达2年，这表明无论治疗结果或自发愈合情况如何，MST反应性持续缺乏。 结论：LCL和BDCL患者治疗前后MST无反应性对DTH作为T细胞介导对亚马逊利什曼原虫（L. (L.) amazonensis）感染抗性标志物的作用提出了挑战。此外，首例由亚马逊利什曼原虫（L. (L.) amazonensis）导致的LCL自发治愈病例在病情缓解前后均未表现出MST反应性，这让人对DTH在此过程中的作用产生怀疑。
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