Serum biomarkers predictive of cure in Chagas disease patients after nifurtimox treatment
1 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
2 Drug for Neglected Diseases initiative (DNDi), Geneva, Switzerland
3 Division of primary care medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
4 Division of international and humanitarian medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
BMC Infectious Diseases 2014, 14:302 doi:10.1186/1471-2334-14-302Published: 3 June 2014
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.
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.
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.
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.