Comparative evaluation of four rapid diagnostic tests that detect human Trypanosoma cruzi-specific antibodies to support diagnosis of Chagas Disease in urban population of Argentina

Background: Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is the most important endemic anthropozoonosis in Argentina. Since 2010, the World Health Organization has highlighted the urgent need to validate diagnostic systems that allow rapid detection of T. cruzi, infection in primary healthcare centers. Serological rapid diagnostic tests (RDTs) for T. cruzi, infection could be used to improve case management, as RDTs do not require specialized laboratories or highly trained staff to use them. We aimed to generate unbiased performance data of RDTs in Argentina, to evaluate their usefulness for improving T. cruzi, diagnosis rates. Methods and principal findings: This is a retrospective, laboratory-based, diagnostic evaluation study to estimate the clinical sensitivity/specificity of four commercially available RDTs for T. cruzi, using the Chagas disease diagnostic algorithm currently used in Argentina as the reference standard. In total, 400 serum samples were tested, 200 from individuals with chronic T. cruzi infection and 200 from individuals not infected with T. cruzi. All results were registered as the agreement of at least two operators who were blinded to the reference standard results. The sensitivity estimates ranged from 92.5–100% (95% confidence interval (CI) lower bound 87.9–98.2%); for specificity, the range was 76–96% (95% CI lower bound 69.5–92.3%). Most RDTs evaluated showed performances comparable with the reference standard method, showing almost perfect concordance (Kappa 0.76–0.92). Conclusions: Our study demonstrates that, under controlled laboratory conditions, commercially available RDTs for CD have a performance comparable to the Argentinian diagnostic algorithm, which is based on laboratory-based serological tests. For the next stage of our work, the RDTs will be evaluated in real-world settings. Author summary: Trypanosoma cruzi is the causative agent of Chagas disease, the most significant transmissible disease between animals and humans in Argentina. It is estimated that two-thirds of individuals with the disease currently reside in urban areas, and globally, only 10% of those affected are aware of their condition. The diagnosis of chronic infection requires conducting at least two different laboratory tests mainly available at reference laboratories, which poses logistical and economic challenges for both the patients and the health systems, and it often results in limited access to high-quality diagnosis. Primary healthcare has the potential to address around 90% of the population’s healthcare needs over their lifetime. Although there are rapid diagnostic tests for T. cruzi infection, that could be potentially incorporated at lower levels of the healthcare system in Argentina, there is a lack of independent evaluation of the available tests. In fact, since 2010 the World Health Organization emphasized the need of evaluating diagnostic tests that enable the rapid detection of T. cruzi infection in primary care centers. In this study, we assessed under controlled laboratory conditions the ability of the rapid diagnostic tests for confirming or ruling out the chronic infection in patients in Argentina.