Chagas Disease Diagnostic Applications

Abstract

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating illness of major significance throughout Latin America, and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stress the necessity of developing new methods operational in Point-of-Care (PoC) settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery.

High-resolution profiling of linear B-cell epitopes from mucin-associated surface proteins (MASPs) of Trypanosoma cruzi during human infections

“…Except for motifs 1 and 2, the rest of the MASP motifs were seldom recognized by chronic Chagasic sera. From a serodiagnosis standpoint, and even if motifs 1 and 2 exhibited relatively good AUC values, their overall performances are not good enough for routine implementation in currently available tests, although their potential applicability in other still unmet diagnostic needs should be further evaluated [ 58 , 59 ]. Finally, it is worth noting that statistically significant correlation between Chagas-chip and ELISA-based data was obtained, hence further validating the applicability of the Chagas-chip platform as a powerful tool for high-throughput identification of relevant T .…”

The Trypomastigote Small Surface Antigen from Trypanosoma cruzi Improves Treatment Evaluation and Diagnosis in Pediatric Chagas Disease

“…Nevertheless, compared to the only similarly designed study that we are aware of, the median times of seronegativization for TSSA (2.21 and 8.67 months for children under and over 8 months of age, respectively) were significantly lower than those recorded for F2/3 (4 and 21.9 months, respectively) (41). As mentioned, F2/3 is so far considered the best alternative serological marker for treatment evaluation in Chagas disease (16,28,29).…”

“…The latter included the evaluation of T. cruzi antigenic fractions or defined antigens that elicit serological responses with different qualitative, quantitative, and/or kinetic properties. Overall, the best results were obtained with the F2/3 fraction (28,29), which consists of highly antigenic ␣-galactosyl epitopes from the surface coat of bloodstream trypomastigotes (30). Several methodological drawbacks (i.e., costly and difficult purification procedures), however, preclude its routine implementation in clinical settings.…”

Treatment of Chagas Disease in the United States

“…A wide range of research initiatives are focusing on the identification of biomarkers, both to help determine which patients are at risk of progression to chronic symptoms and to measure the effectiveness of antitrypanosomal therapy [ 77 – 79 ]. Finally, development of new diagnostic tools with high specificity and sensitivity, consistent in different patient populations and T. cruzi genetic strains, will greatly facilitate widespread screening [ 80 ].…”