Breakthrough in sleeping sickness diagnosis

The University of Geneva in Switzerland is not historically known to have been involved in research on human African trypanosomiasis, or sleeping sickness, but rather on brain damage biomarkers. Yet, the recent interest in the disease by Dr. Jean-Charles Sanchez, head of the Biochemical and Proteomics Research Group (BPRG) at the university, could have provided the closest indication so far that it is possible to accurately distinguish the early and late stages of the disease. Dr. Sanchez and his team were carrying out analysis on cerebrospinal fluid (CSF) from 100 sleeping sickness patients when they discovered that a number of molecules were consistently elevated in patients who were in late stage disease. Among 16 molecules studied, IP-10 could distinguish between early and late stage patients with a sensitivity of 91% and a specificity of 100%. (Abstract)

While this discovery was significant on its own, more exciting information was generated when the scientists used statistical methods to determine what would happen if they combined the results of two or more molecules. The outcome was a panel of three molecules, IP-10, GSTP1 and IL-8, which together distinguished late stage patients with a sensitivity of 97% and a specificity of 100%. Details of these findings will be published and made broadly available as soon as possible.

The project is a collaborative effort with Makerere University in Uganda and the Institute of Tropical Medicine (ITM) in Belgium, and is funded by FIND. Dr. Joseph Ndung’u, head of the HAT Diagnostics programme at FIND, remarked: “It has been a hard nut to crack, something which needed the right brains and appropriate back-up, and we are very proud to be providing the back-up.”

Dr. Sanchez expressed satisfaction that while in the past most of his group’s research has focused mainly on brain diseases that affect the western world, they are finally involved in work that could mean a lot to millions of under-privileged people in the rural areas of Africa, who live under constant threat of infection. However, he cautions that it is still too early to shout “victory” as the work needs to be repeated on a new and larger multicentric set of samples before definite conclusions can be made.

When people get sleeping sickness, it gradually progresses from an early (stage 1) to late stage (stage 2) form. In the early stage, parasites are found in the blood and other organs, except the brain, and treatment is relatively cheap and safe. If treatment has not been carried out, however, the parasites eventually enter the brain, causing late stage disease, which is more difficult and risky to treat, because the patients are by then in a bad state, and the drugs are themselves quite toxic.

At present, the only way to distinguish between early and late stage sleeping sickness is by performing a lumbar puncture, followed by an examination of the CSF for parasites, and counting the number of white cells. Parasites are usually found in very low numbers in the CSF of patients, and therefore difficult to see under a microscope. While large numbers of white cells are a good indicator of late stage disease, the cut-off for a patient to be considered as early stage is vague. In situations like this, the clinician is faced with the difficult task of deciding whether to expose the patient to risky treatment or not. A more specific or exact test will therefore be of immense importance in the management of cases, and after treatment, confirmation of cure.

For FIND, the ultimate goal is to develop a test for staging patients that would not require a lumbar puncture, an uncomfortable procedure that exposes patients to other risks, such as bacterial infections, epidural bleeding or trauma to the spinal chord. This objective demands intensified efforts and the involvement of more partners, six of whom are already engaged in this initiative.

Photo courtesy of Dr. Jean-Charles Sanchez

The scientific team, under the guidance of Dr. Sanchez, who identified the set of molecules associated with late stage sleeping sickness
From left to right: Xavier Robin, Jean-Charles Sanchez, Natalia Tiberti, Loic Dayon, Feliciano Priego-Capote, Natacha Turck, Alexandre Hainard, Domitille Schvartz, Yohann Couté, Yannick Brunner, and Catherine Fouda. Not pictured: Nadia Walter

Scientists make major breakthrough in staging sleeping sickness