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

Abstract

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 suitability of neopterin and CXCL13 as disease stage biomarkers and monitors of treatment efficacy 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). Upon relapse, the animals were treated curatively with melarsoprol (Mel B) from 82 dpi. Blood and cerebrospinal fluid (CSF) samples were collected weekly and assessed for parasitosis, as well as tested for neopterin and CXCL13 by ELISA, for a period of 39 weeks. Results Neopterin concentrations 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. Levels dropped upon sub-curative treatment with DA. CXCL13 concentrations 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 CSF neopterin and CXCL13 peak levels coinciding 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.