Use of rapid diagnostic tests (RDTs) for conclusive diagnosis of chronic Chagas disease – field implementation in the Bolivian Chaco region

Abstract

Chagas disease, caused by the parasite Trypanosoma cruzi, is the neglected tropical disease with a highest burden in Latin America. Its acute stage is mostly asymptomatic and goes unnoticed. Symptoms appear at the chronic stage, which is when diagnosis is usually made. This is based on the agreement of two conventional serological tests such as Enzyme-Linked Immunosorbent Assays (ELISAs). There are commercial kits with good sensitivity and specificity but their use is impractical in many highly endemic regions with poorly equipped laboratories. Luckily, several rapid diagnostic tests (RDTs) are available for the detection of anti-T. cruzi immunoglobulins. They are easy to operate, require no cold storage, provide fast turnaround of results, and some can work with a tiny volume of whole blood as sample. With the aim to field validate their use we compared an alternative algorithm based on a combination of RDTs with the standard based on ELISAs. In both cases a third test was available in case of discordance. RDTs were implemented by mobile teams in field campaigns to detect chronic T. cruzi-infections in the Chaco region of Bolivia. ELISAs were made in the reference laboratories located in the main hospitals of Yacuiba and Villa Montes, two major cities of the region. We enrolled 685 subjects who voluntarily participated in the study and had not been treated against the disease before. The agreement between the two main RDTs was 93.1% (638/685) (kappa index = 0.86; CI 95% 0.83–0.90). In comparison to the ELISAs algorithm, the combined use of the RDTs provided a sensitivity of 97.7% and a specificity of 96.1%. These results support the use of RDTs for the diagnosis of chronic Chagas disease in the studied region, and encourage their evaluation in other regions of Bolivia and other endemic countries.

Sensitivity and Specificity of two rapid tests for the diagnosis of infection by Trypanosoma cruzi in a Colombian population

“…As it is important to interpret results in the context of the prevalence of the disease [ 47 ], these diagnostic indices have considerable inverse variation, as increasing prevalence increases PPV and decreases NPV and vice-versa [ 46 ]. In the present study, the results obtained in the PPV in CDP were 97.8%, and they were 100% for CSP; and in the NPV the two RDT’s were 100%, observing that the two RDT’s presented a high probability of returning a correct diagnosis, which coincides with the findings of Eguez et al [ 26 ] and Lozano et al [ 34 ]. The likelihood ratio results showed that the RDT’s correctly measured the probability of a concrete result (positive or negative) according to the presence or absence of CD.…”

“…As for the CSP, there was a sensitivity and specificity of 100%, which was similar to that described in Latin American migrants to Switzerland, who had values of 95.2% and 99.9% [ 41 ]; in Argentina with values of 95.3% and 99.5% [ 42 ]; in Bolivia, according to information from Rody et al in 2008 with values of 93.4% and 99.0% [ 43 ] and by Lozano et al in 2019 with values of 97.7% and 97.4%, respectively [ 34 ], they described DE of 97.5% similar to the results of the present study in that CSP was able to correctly classify 100% of the participants evaluated.…”

“…In several studies [ 26 , 34 , 40 , 50 ], the results of evaluation of the diagnostic exactness of the RDT’s have suggested the use of these tests for the detection and monitoring of CD. These tests deliver results rapidly without the need for electrical equipment, utilizing small volumes of whole blood for samples, and can be completed anywhere (that is to say, in any region).…”

“…There are several RDT’s for detecting infection by T . cruzi which have the advantages described above over conventional tests and that have high sensitivities and specificities according to several authors [ 26 , 33 , 34 ]. Thus, in the present study, all samples were analyzed using two immunochromatographic diagnostic tests based on different antigens: Chagas Detect Plus (InBios International Inc., Seattle, USA) CDP [ 35 ], which uses a multi-epitope antigen, and Chagas Stat-Pak (Chembio Inc., Medford USA) CSP [ 36 ], which employs a combination of recombinant proteins.…”

Rapid Diagnostic Tests for Trypanosoma cruzi Infection: Field Evaluation of Two Registered Kits in a Region of Endemicity and a Region of Nonendemicity in Argentina

“…In the present study, the SD RDT showed a sensitivity of 97%, similar to that obtained with serum samples but with a direct sample of whole blood. A recent field study performed in Bolivia using finger prick whole-blood samples with two RDTs showed sensitivity values of 97.7% and 98.4% ( 24 ). These results are similar to the results of the SD test obtained in our study, but in the case of the Bolivian study, the gold standard was two ELISAs, which may show higher sensitivity and lower specificity ( 25 ), while in our study, the gold standard was based on the standard diagnostic recommended by the PAHO.…”