Matrix metalloproteinase-9 and intercellular adhesion molecule 1 are powerful staging markers for human African trypanosomiasis

A Hainard, N Tiberti, X Robin, DM Ngoyi, E Matovu, JC Enyaru, M Müller, N Turck, JM Ndung'u, V Lejon, JC Sanchez

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    Objectives A critical step before treatment of human African trypanosomiasis (HAT) is the correct staging of the disease. As late stage is established when trypanosomes cross the blood-brain barrier and invade the central nervous system, we hypothesized that matrix metalloproteinases and cell adhesion molecules could indicate, alone or in combination, the disease progression from the first to the second stage of HAT. Methods We measured the levels of MMP-2, MMP-9, ICAM-1, VCAM-1 and E-selectin in the cerebrospinal fluid (CSF) of 63 Trypanosoma brucei gambiense-infected patients (15 stage 1 and 48 stage 2). Staging was based on counting of white blood cells (WBC) and/or parasite detection in CSF. Concentrations were obtained either by ELISA or multiplex bead suspension assays, and results were compared with three known HAT staging markers (CXCL10, CXCL8 and H-FABP). Results ICAM-1 and MMP-9 accurately discriminated between stage 1 and stage 2 patients with HAT with 95% sensitivity (SE) for 100% specificity (SP), which was better than CXCL10 (93% SE for 100% SP), one of the most promising known markers. Combination of ICAM-1 and MMP-9 with H-FABP provided a panel that resulted in 100% of SE and SP for staging HAT. Conclusions ICAM-1 and MMP-9, alone or in combination, appeared as powerful CSF staging markers of HAT. Final validation of all newly discovered staging markers on a large multi-centric cohort including both forms of the disease as well as patients with others infections should be performed.
    Original languageEnglish
    JournalTropical Medicine and International Health
    Volume16
    Issue number1
    Pages (from-to)119-126
    Number of pages8
    ISSN1360-2276
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Protozoal diseases
    • Sleeping sickness
    • Trypanosomiasis-African
    • Trypanosoma brucei gambiense
    • Vectors
    • Tsetse flies
    • Glossina morsitans
    • Disease progression
    • Staging
    • Markers
    • Molecular markers
    • Cerebrospinal fluid
    • CSF
    • White blood cell count
    • Parasite detection
    • MMP-2
    • MMP-9
    • ICAM-1
    • VCAM-1
    • E-selectin
    • CXCL10
    • CXCL8
    • H-FABP
    • Specificity
    • Sensitivity
    • Laboratory techniques and procedures

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