title: Serum biomarkers predictive of cure in Chagas disease patients after nifurtimox treatment.
abstract: BACKGROUND
  Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, remains an important public health issue in many Central and South American countries, as well as non-endemic areas with high rates of immigration from these countries. Existing treatment options for CD are limited and often unsatisfactory. Moreover the lack of post-treatment tests of cure limits the development of new drugs. To address this issue, we sought to identify serum biomarkers following nifurtimox (Nfx) treatment that could be used as an early test of cure and/or markers of a therapeutic response.
  
  
  METHODS
  Human sera from Chagas patients pre- and post-treatment with Nfx (n = 37) were compared to samples from healthy subjects (n = 37) using a range of proteomic and immunologic techniques. Biomarker peaks with the best discriminatory power were further characterized.
  
  
  RESULTS
  Using serum samples (n = 111), we validated the presence of five key biomarkers identified in our previous study, namely human apolipoprotein A-I (APOA1) and specific fragments thereof and one fragment of human fibronectin (FN1). In chagasic serum samples all biomarkers except full-length APOA1 were upregulated. These five biomarkers returned to normal in 43% (16/37) of the patients treated with Nfx at three years after treatment.
  
  
  CONCLUSIONS
  The normalization of biomarker patterns strongly associated with CD suggests that these markers can be used to identify patients in whom Nfx treatment is successful. We believe that these are the first biomarkers predictive of cure in CD patients.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Santamaria
authors.forename: Eric
authors.initials: E
authors.lastname: Chatelain
authors.forename: Yves
authors.initials: Y
authors.lastname: Jackson
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Miao
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.forename: François
authors.initials: F
authors.lastname: Chappuis
authors.affiliation: National Reference Center for Parasitology, Research Institute of the McGill University Health Centre, Department of Medicine, Division of Infectious Diseases, Montreal General Hospital, 1650 Cedar Ave,, Room R3-137, Montreal, Quebec H3G 1A4, Canada. momar.ndao@mcgill.ca.
authors.forename: Momar
authors.initials: M
authors.lastname: Ndao
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D014355:Chagas Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D008297:Male; D009547:Nifurtimox / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D013020:South America; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D015415:Biomarkers; D005353:Fibronectins; D014344:Trypanocidal Agents; D009547:Nifurtimox