Novel markers for treatment outcome in late-stage Trypanosoma brucei gambiense trypanosomiasis.
BACKGROUND
To date, no biological marker for treatment outcome in human African trypanosomiasis (HAT) has been described. The accuracy of biological markers for prediction of treatment outcome of HAT caused by Trypanosoma brucei gambiense was assessed.


METHODS
Cerebrospinal fluid (CSF) white blood cell (WBC) count and immunoglobulin M (IgM), trypanosome-specific antibody, total protein, and interleukin-10 levels were determined before and up to 24 months after treatment of late-stage HAT.


RESULTS
Treatment failure was experienced by 48 of 260 patients. Pretreatment CSF WBC counts > or = 102 cells/microL, IL-10 concentrations > or = 37 pg/mL, LATEX/IgM end titers > or = 1:32, LATEX/T. b. gambiense end titers > or = 1:2, and protein concentrations > or = 674 mg/L were associated with treatment failure. Six months after treatment, patients with CSF WBC counts < or = 5 cells/microL were at low risk of HAT recurrence (negative predictive value, >0.93). After 12 months, the combination of CSF WBC count > or = 8 cells/microL and LATEX/IgM end titer > or = 1:4 predicted treatment failure with 97% specificity and 79% sensitivity. Eighteen months after treatment, each marker accurately predicted treatment outcome. The combination of CSF WBC count > or = 8 cells/microL and LATEX/IgM end titer > or = 1:4 was 100% specific for treatment failure after 18 and 24 months.


CONCLUSIONS
HAT-affected patients with elevated pretreatment CSF levels of WBC, interleukin-10, IgM, trypanosome-specific antibody, and total protein are at risk of treatment failure. Six months after treatment, patients with CSF WBC counts < or = 5 cells/microL can be considered to be cured. The assessment of a combination of CSF WBC count and LATEX/IgM level allowed accurate prediction of outcome beginning at 12 months after treatment, as did each individual marker at 18 months after treatment.
Lejon
Veerle
V
Department of Parasitology, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerpen, Belgium. vlejon@itg.be
Roger
Isabelle
I
Mumba Ngoyi
Dieudonné
D
Menten
Joris
J
Robays
Jo
J
N'siesi
Francois X
FX
Bisser
Sylvie
S
Boelaert
Marleen
M
Büscher
Philippe
P
D000818:Animals; D000913:Antibodies, Protozoan / Q000134:cerebrospinal fluid; D015415:Biomarkers; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000134:cerebrospinal fluid; D016753:Interleukin-10 / Q000134:cerebrospinal fluid; D007958:Leukocyte Count; D008549:Melarsoprol / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011506:Proteins / Q000032:analysis; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000627:therapeutic use; D014347:Trypanosoma brucei gambiense / Q000302:isolation & purification*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology*
D000913:Antibodies, Protozoan; D015415:Biomarkers; D007075:Immunoglobulin M; D011506:Proteins; D014344:Trypanocidal Agents; D016753:Interleukin-10; D008549:Melarsoprol