Development of a Multiplexed Assay for Detection of Leishmania donovani and Leishmania infantum Protein Biomarkers in Urine Samples of Patients with Visceral Leishmaniasis

被引:0
|
作者
Abeijon, Claudia [1 ]
Alves, Fabiana [2 ]
Monnerat, Severine [2 ]
Wasunna, Monique [3 ]
Mbui, Jane [3 ]
Viana, Agostinho G. [4 ]
Bueno, Lilian L. [4 ]
Siqueira, Williane F. [4 ]
Carvalho, Silvio G. [5 ]
Agrawal, Neha [6 ]
Fujiwara, Ricardo [4 ]
Sundar, Shyam [7 ]
Campos-Neto, Antonio [1 ,8 ]
机构
[1] DetectoGen Inc, Grafton, MA 01536 USA
[2] Drugs Neglected Dis Initiat, Geneva, Switzerland
[3] KEMRI Ctr Clin Res, Nairobi, Kenya
[4] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil
[5] Univ Estadual Montes Claros, Montes Claros, MG, Brazil
[6] Temple Univ, Philadelphia, PA 19122 USA
[7] Banaras Hindu Univ, Inst Med Sci, Varanasi, Uttar Pradesh, India
[8] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA 01536 USA
基金
美国国家卫生研究院;
关键词
antigen detection test; antigenuria; Leishmania donovani; Leishmania infantum; visceral leishmaniasis; AZAR DERMAL LEISHMANIASIS; POLYMERASE-CHAIN-REACTION; DIAGNOSTIC-TESTS; RECOMBINANT K-39; ANTIGEN; IDENTIFICATION; CARRIERS; BLOOD;
D O I
10.1128/JCM.02076-18
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Visceral leishmaniasis (VL) is a serious and fatal disease caused by the parasites Leishmania infantum and Leishmania donovani. The gold standard diagnostic test for VL is the demonstration of parasites or their DNA in spleen, lymph node, or bone marrow aspirates. Serological tests exist but cannot distinguish active VL from either prior exposure to the parasites or previously treated VL disease. Using mass spectroscopy, we have previously identified three L. infantum protein biomarkers (Li-isd1, Li-txn1, and Li-ntf2) in the urine of VL patients and developed a sensitive and specific urine-based antigen detection assay for the diagnosis of VL that occurs in Brazil (where VL is caused by L. infantum). However, unpublished observations from our laboratory at DetectoGen showed that these biomarkers were detected in only 55% to 60% of VL patients from India and Kenya, where the disease is caused by L. donovani. Here, we report the discovery and characterization of two new biomarkers of L. donovani (Ld-mao1 and Ld-ppi1) present in the urine of VL patients from these two countries. Capture enzyme-linked immunosorbent assays using specific rabbit IgG and chicken IgY were developed, and the assays had sensitivities of 44.4% and 28.8% for the detection of Ld-mao1 and Ld-ppi1, respectively. In contrast, a multiplexed assay designed to simultaneously detect all five leishmanial biomarkers markedly increased the assay sensitivity to 82.2%. These results validate the utility of leishmanial protein biomarkers found in the urine of VL patients as powerful tools for the development of an accurate diagnostic test for this disease.
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页数:13
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