Serodiscordance in chronic Chagas disease diagnosis: a real problem in non-endemic countries

Abstract

According to the WHO, chronic Chagas disease (CD) diagnosis is based on two serological techniques. To establish a definitive diagnosis, the results must be concordant. In cases of discordances, the WHO proposes repeating serology in a new sample, and if results remain inconclusive, a confirmatory test should be performed. This study, conducted at two Tropical Medicine Units in Europe over 4 years, aims to assess the diagnostic yield of TESA- (trypomastigote excreted-secreted antigens) blot as a confirmatory technique in patients with inconclusive and discordant results. Of 4939 individuals screened, 1124 (22.7%) obtained positive results and 165 (3.3%) discordant results. Serology was repeated in 88/165 sera and discrepancies were solved in 25/88 (28.4%) cases. Patients without a definitive diagnosis were classified in two different groups: Group 1, including patients with inconclusive results despite retesting (n = 63), and Group 2, including patients with discordant results not retested (n = 77). TESA-blot was performed for all of Group 1 and 39/77 of Group 2 and was positive for 33/63 (52.4%) and 21/39 (53.8%), respectively. Analysis of Group 1 results showed a moderate agreement between results of the ELISA based on native antigen and TESA-blot (κ 0.53). In contrast, a clear disagreement was observed between the ELISA based on recombinant antigens and TESA-blot (κ <0). A sizeable proportion of patients are suspected to have CD with inconclusive results or in whom re-testing is not feasible. TESA-blot was positive in half of these patients, highlighting the need for a confirmatory assay in European centres caring for exposed individuals.

Usefulness of the ARCHITECT Chagas® assay as a single test for the diagnosis of chronic Chagas disease

“…is co‐endemic with Chagas disease. In comparison with other studies, our initial discordant results were high (18%), although, following WHO guidelines, most were subsequently resolved with a third serological test or a second sample .…”

“…Some 87 000 of these immigrants are estimated to be potentially infected with T. cruzi , which means that screening this population could provide a clue to treating and preventing cardiac and digestive complications and avoiding congenital transmission . Spanish studies have recorded the seroprevalence of Chagas disease among Latin American immigrants as ranging from 2.5% to 22.3% , while our study obtained a seroprevalence of 7.39%. Compared with other European countries, our seroprevalence was not as high as previously reported .…”

Estimating the current burden of Chagas disease in Mexico: a systematic review of epidemiological surveys from 2006 to 2017

“…A total of 38 studies were identified, covering most of the country with the notable exception of the state of Michoacán. Discrepancies in previous studies have been often attributed to diagnostic methods and uncertainties about the confirmation of cases [57], leading to current recommendations of health agencies requesting a minimum of 2 serological techniques for accurate diagnostic [10]. Based on this criterion, we found a national seroprevalence of T. cruzi infection of 2.26%, corresponding to 2.71 million cases in the country.…”

High sensitivity and reproducibility of in‐house ELISAs using different genotypes of Trypanosoma cruzi

“…However, there are no routine prenatal screening programs . A study conducted recently in Europe in a population of 4939 individuals recommended the use of the TESA‐blot as a confirmatory test in order to resolve the discrepant results between diagnostic tests that use total or recombinant antigens …”

“…Currently, the TESA-blot assay is being considered as a possible confirmatory test for the diagnosis of Chagas disease. 26,59 The sensitivity and specificity of this test has been evaluated by several studies in different geographical regions of South America, showing 100% for both parameters. In addition, TESA-blot is also used to resolve inconclusive cases due to its high reproducibility and accuracy.…”