title: A link between chemokine levels and disease severity in human African trypanosomiasis.
abstract: Trypanosoma brucei gambiense infection is an important public health challenge in sub-Saharan Africa. This parasitic disease is difficult to diagnose due to insidious clinical signs and transient parasitaemias. The clinical course is marked by two stages of increasing disease severity. An early systemic parasitic invasion is followed by the development of a progressive meningo-encephalitis. During this latter stage, a broad spectrum of neurological signs appears, which finally lead to a demyelinating and fatal stage if untreated. Treatment is toxic and difficult to administer when the CNS is invaded. Therefore, accurate diagnostic methods for stage determination are needed. The classically used criteria are not sufficiently specific and mechanisms of parasite invasion through the blood-brain barrier remain poorly understood. As cytokines/chemokines are involved in the early recruitment of leukocytes into the CNS, this study has focused on their potential value to define the onset of CNS involvement. Levels of monocyte chemoattractant protein-1/CCL-2, macrophage inflammatory protein-1alpha/CCL-3, IL-8/CXCL-8, regulated upon activation T cell expressed and secreted (RANTES)/CCL-5 and IL-1beta were measured in paired sera and CSF from 57 patients and four controls. Patients were classified into three groups (stage 1, intermediate and stage 2) according to current field criteria for stage determination (CSF cell count, presence of trypanosomes in CSF and neurological signs). In sera, cytokine/chemokine levels were poorly related to disease stage. Only CXCL-8 was higher in stage 1 patients when compared with stage 2 and CCL-5 was higher in controls when compared with patients. In contrast, in CSF the expression of the selected cytokines, except CCL-5, was associated with the presence of neurological signs, demonstrating their diagnostic value. We observed a relationship between the presence of trypanosomes or trypanosome-related compounds in CSF and levels of IL-1beta, CXCL-8, CCL-2 and CCL-3. These cytokines and chemokines may be triggered by the parasite and hence are potential markers of CNS invasion.
authors.affiliation: Equipe Accueil 3174 Neuroparasitologie et Neuroépidémiologie Tropicale, Institut d'Epidémiologie Neurologique et de Neurologie Tropicale, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges Cedex, France. bertrand.courtioux@unilim.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Courtioux
authors.forename: Caroline
authors.initials: C
authors.lastname: Boda
authors.forename: Gédéon
authors.initials: G
authors.lastname: Vatunga
authors.forename: Lynda
authors.initials: L
authors.lastname: Pervieux
authors.forename: Théophile
authors.initials: T
authors.lastname: Josenando
authors.forename: Paulette Mengue
authors.initials: PM
authors.lastname: M'Eyi
authors.forename: Bernard
authors.initials: B
authors.lastname: Bouteille
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Jauberteau-Marchan
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bisser
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier; D020808:Central Nervous System Protozoal Infections / Q000175:diagnosis*; D018925:Chemokines / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D002648:Child; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008875:Middle Aged; D012720:Severity of Illness Index; D014347:Trypanosoma brucei gambiense / Q000302:isolation & purification*; D014353:Trypanosomiasis, African / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines