Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives

Abstract

The definition of a biomarker provided by the World Health Organization is any substance, structure, or process that can be measured in the body, or its products and influence, or predict the incidence or outcome of disease. Currently, the lack of prognosis and progression markers for chronic Chagas disease has posed limitations for testing new drugs to treat this neglected disease. Several molecules and techniques to detect biomarkers in Trypanosoma cruzi-infected patients have been proposed to assess whether specific treatment with benznidazole or nifurtimox is effective. Isolated proteins or protein groups from different T. cruzi stages and parasite-derived glycoproteins and synthetic neoglycoconjugates have been demonstrated to be useful for this purpose, as have nucleic acid amplification techniques. The amplification of T. cruzi DNA using the real-time polymerase chain reaction method is the leading test for assessing responses to treatment in a short period of time. Biochemical biomarkers have been tested early after specific treatment. Cytokines and surface markers represent promising molecules for the characterisation of host cellular responses, but need to be further assessed.

Chagas Disease Diagnostic Applications

“…Overall, and despite multiple and disparate attempts, none of the serological and/or biochemical markers that have been explored so far translated into a reliable, easy to assay and interpret marker to asses cardiac damage and/or disease prognosis (recently reviewed in (Pinazo et al, 2015)). The complex and likely multifactorial nature of Chagas disease pathogenesis together with intrinsic difficulties in establishing appropriate experimental/epidemiological models converge in turning this area as the most challenging in terms of T. cruzi biomarker discovery.…”

Bug Smash, Bug Splash: A Case Report of an Unusual Transmission of American Trypanosomiasis with a Brief Review of the Literature

“…However, T. cruzi amastigotes can be found in tissues, especially in cardiac and skeletal muscle [11]. The amplification of T. cruzi DNA using polymerase chain reaction is the leading test for assessing response to treatment in a short period of time, in contrast with microscopy, which lacks sensitivity, and blood cultures, which can take up to 30 days and have a higher rate of false-negative results [12,13]. Currently, there are no biomarkers to assess the therapeutic response in chronic Chagas disease [13].…”

“…The amplification of T. cruzi DNA using polymerase chain reaction is the leading test for assessing response to treatment in a short period of time, in contrast with microscopy, which lacks sensitivity, and blood cultures, which can take up to 30 days and have a higher rate of false-negative results [12,13]. Currently, there are no biomarkers to assess the therapeutic response in chronic Chagas disease [13]. The diagnosis of the acute phase of the disease is difficult due to the mild symptoms; it is diagnosed in less than 10% of patients who have this phase of Chagas disease [14].…”

Purification of Glycosylphosphatidylinositol-Anchored Mucins from Trypanosoma cruzi Trypomastigotes and Synthesis of α-Gal-Containing Neoglycoproteins: Application as Biomarkers for Reliable Diagnosis and Early Assessment of Chemotherapeutic Outcomes of Chagas Disease

“…Therefore, lack of reliable biomarkers (BMKs) for assessment of therapeutic efficacy following chemotherapy is a major challenge in ChD. Other major challenges include the lack of effective epidemiological and insect-vector control, accurate diagnosis, and a prophylactic or therapeutic vaccine [12,4,13]. …”