Нейроинфекционные заболевания

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Cerebrospinal Fluid Neopterin and CXCL13 are Suitable Biomarkers for Staging and Detection of Treatment Failure in a Non-Human Primate Model of Human African Trypanosomiasis

Dawn N Maranga, Maina J Ngotho, Victor M Mwadime, Thomas A Adino, John Kagira, Maxwell Waema, George A Omondi, Sylvain Biéler and Joseph M Ndungu

Background: Follow-up of treated human African trypanosomiasis (HAT) patients has been a routine practice for confirming cure and early detection of treatment failure.

Objective: The aim of this study was to verify whether the neopterin and CXCL13 biomarkers are suitable for determining the stage of disease, and for monitoring the efficacy of treatment in a vervet monkey model of HAT.

Methods: Six monkeys were infected with Trypanosoma brucei. Late stage disease was induced by sub-curative treatment with diminazene aceturate (DA) from 28 days’ post-infection (dpi). When relapses occurred, the animals were treated curatively with melarsoprol (Mel B) from 82 dpi. Blood and cerebrospinal fluid (CSF) samples were collected at weekly intervals and assessed for parasitosis, as well as tested for neopterin and CXCL13 by ELISA, for a period of 39 weeks.

Results: The concentration of neopterin in serum increased rapidly after infection in early disease (stage 1), peaking at 14 dpi. Levels then dropped rapidly to pre-infection levels by 35 dpi. In contrast, there was a marginal increase in CSF neopterin during early infection, with a minor peak at 21 dpi. Serum CXCL13 increased rapidly from 7 dpi, peaking at 28 dpi, after which the levels dropped upon sub-curative treatment with DA. The concentration of CXCL13 in CSF also increased gradually in early stage disease and continued to rise after sub-curative treatment with DA. Curative treatment with Mel B resulted in its gradual decline, reaching pre-infection levels 105 days later.

Conclusions: The changes in CSF neopterin and CXCL13 correspond to important time-points and stages of the disease. That peak levels coincided with time of relapses demonstrates the potential of these biomarkers in staging and detecting treatment failure. Moreover, the rapid fall in CSF neopterin after curative treatment confirms its great potential for use in development of a test of cure.