Developing tools for disease staging

Diagnosis of sleeping sickness involves case detection followed by staging, which is crucial in the decision of the treatment to be given. In the early stage of the disease, also referred to as Stage I, the infection is confined to the haemolymphatic system. In the second or late stage, the parasites have penetrated the central nervous system (CNS) and, depending on the duration of the infection, the CNS would be at various stages of damage.

To distinguish the two stages, a lumbar puncture is performed and the cerebrospinal fluid (CSF) is examined for presence of parasites and elevated number of white cells (Figure 1). These parameters suffer from insufficient sensitivity and, in the case of white cell count, of specificity as well. Moreover, the two diagnostic approaches are hampered by technical problems, including controversy over cut-off values. Due to these shortcomings, the invasive character of lumbar puncture and toxicity of drugs used to treat the late stage, improved markers for staging are desperately needed.

After treatment is completed, patients are followed up for a period of 24 months to confirm that they have been cured. Since relapses are mainly of CNS origin, and parasites are often difficult to find in blood, follow-up mainly relies on lumbar puncture and CSF examination (Figure 2).

Figure 1: Undergoing a painful lumbar puncture in a patient whose blood was positive for parasites (photo courtesy of WHO)

Figure 2: Counting white cells in a CSF sample to determine whether the patient is in early or late stage disease. Treatment varies depending on the stage of disease (photo courtesy of WHO)

FIND is working with partners on projects to determine the feasibility of developing new tests for staging sleeping sickness with improved accuracy to guide treatment, and for follow-up to determine treatment success. Special attention is being given to speed, simplicity, cost, and reliability of the new tests, as well as reduced invasiveness.

Search for blood markers for late stage sleeping sickness
Partner organization: Aberdeen University, U.K.
More

In search of biomarkers for staging sleeping sickness
Partner organizations: University of Geneva, Switzerland; Institute of Tropical Medicine, Antwerp; Makere University, Uganda
More

A clinical study to define markers for staging in human African trypanosomiasis
Partner organizations: Institute of Tropical Neurology, Limoges, France Instituto de Combate e Controlo das Tripanossomiases, Angola
More

Development of a single format test for IgM quantification in CSF of sleeping sickness patients
Partner organizations: Institute of Tropical Medicine, Antwerp; Royal Tropical Institute, Amsterdam
More