Parasites in the brain? The search for sleeping sickness biomarkers

Evaluation of: Tiberti N, Hainard A, Lejon V et al. Cerebrospinal fluid neopterin as marker of the meningo-encephalitic stage of Trypanosoma brucei gambiense sleeping sickness. PLoS ONE 7(7), e40909 (2012). Human African trypanosomiasis (HAT) is a fatal parasitic disease that progresses from an early stage (stage 1), where parasites multiply in the hemolymphatic system, to a late stage (stage 2) disease, where parasites have become manifest within the CNS. Patients with stage 1 disease are treated with relatively safe drugs, but stage 2 disease requires treatment with drugs that are very toxic or difficult to administer. Thus, it is important to determine the stage of HAT infection before treating. HAT staging currently involves microscopic examination of cerebrospinal fluid (CSF), looking for the presence of parasites, or for more than five white blood cells per microliter CSF. This article tested the specificity and selectivity of eight potential CSF markers for stage 2 HAT, by analysis of levels in 400 CSF samples from patients diagnosed with stage 1 or stage 2 HAT by WHO protocols. Two of these markers gave results that were comparable with those obtained by conventional diagnosis. The potential for and challenges of developing improved staging for HAT are discussed.