Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review

Abstract

This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.

Keywords::

• apolipoprotein A1
• biomarker
• Chagas
• cure
• lytic antibodies
• prothrombotic
• progression
• selenium
• serology
• trypanosomiasis

Acknowledgements

The COHEMI project study group includes: Maurizio Bonati, Francesca Severino, Valeria Confalonieri, Chiara Pandolfini, Zeno Bisoffi, Dora Buonfrate, Andrea Angheben, Marco Albonico, Alessandro Bartoloni, Marianne Strohmeyer, Lorenzo Zammarchi, Jose Muñoz, Robert Pool, Ana Requena-Mendez, Maria Roura, Joaquim Gascón, Mª Jesús Pinazo, Mª Elizabeth Posada, Anita Hardon, Christopher Pell, Peter L. Chiodini, Juan Moreira, Roberto Sempértegui, Mariella Anselmi, Eduardo Gotuzzo, Maria Alejandra Mena, Hector H. Garcia, Javier Bustos, Saul Santiva, Faustino Torrico, Daniel Lozano, Guido Chumiray Rojas, Teresa Hinojosa Cabrera, Javier Ochoa Morón, Ignacio Abapori, Cuellar, Jaime Amorós Suarez, Gianni Tognoni, Alessandra Nicoletti, Elisa Bruno.

Financial & competing interests disclosure

This work has been supported by the EC within the 7th Framework Program under grant agreement nu FP7–GA-261495. The CRESIB Research group receives funds from AGAUR, (project 2009SGR385) and also from the project RICET (RD12/0018/0010) within the Spanish National plan of R+D+I and co-funded by ISCIII-Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Major gaps in current knowledge about Trypanosoma cruzi infection are:

  • ○ how to identify patients who will progress to cardiopathy;

  • ○ how to identify patients who although being asymptomatic, have an incipient cardiopathy that requires strict follow-up and

  • ○ how to identify in a reasonably short time those patients who are cured after antiparasitic therapy.

• • An ideal biomarker to predict progression of the Chagas disease would be one that if the test results negative, progression should be reasonably ruled out and the patient neither should be treated nor should be periodically followed-up.

• • An ideal biomarker to detect early stages of cardiac or gastrointestinal disease is one that if the result of the test is positive, the patient should be closely monitored to better manage future complications of the disease.

• • Natriuretic peptides are to date the most accepted markers in the scientific community that can detect early cardiac damage.

• • Apolipoprotein A1 (Apo A1) appears as a potential negative biomarker in Chagas disease. This biomarker could be used as both an indicator of progression and follow-up.

• • To better evaluate the efficacy of the biomarkers detecting early progression, more prospective studies undertaken in indeterminate patients with Chagas disease and with a larger follow-up are required.

• • Cure biomarkers are crucial to assess the efficacy of the antiparasitic drugs in clinical trials.

• • Chronic T. cruzi infections do not have a recognized gold standard cure marker.

• • Prothrombotic biomarkers, lytic antibodies and other antibodies based on recombinant antigens of T. cruzi appear to be useful as cure markers.