Definition of a diagnostic routine in individuals with inconclusive serology for chagas disease

Abstract

Despite the existence of highly sensitive tests, inconclusive serological results are frequent in chronic chagasic infection. This study aimed to define a diagnostic conduct for 30 individuals with inconclusive serology (G3) for chagasic infection assisted at the Outpatient Unit for Infectious and Parasitic Diseases of the Botucatu School of Medicine. Twenty-one individuals with negative serology (G1) and 33 with positive serology (G2) were also studied. Serological methods ELISA, HAI, IFI and immunoblotting TESA-cruzi were used for G1, G2 and G3, and parasitological methods xenodiagnosis, hemoculture and PCR-LIT were used for G2 and G3 individuals. ELISA, HAI and IFI were performed in 5 different blood samples in G2 and G3. TESA-cruzi was carried out only once in G1, G2 and G3 and, since it is the most sensitive, it was utilized as standard. In G3, positivity for ELISA reached 86% in the fifth blood sample; the ELISA+HAI+IFI combination showed a maximum of 44.8% in the second sample; and TESA-cruzi, 76% in one single sample. Xenodiagnosis positivity was 9.4%; hemoculture showed 15.2%; and PCR-LIT exhibited 22% positivity in G2. Nevertheless, in G3, positivity percentage was 3.4% for xenodiagnosis, 6.7% for PCR-LIT, and no positive result was found for hemoculture. In G3, PCR-LIT resolved one case which was still inconclusive according to serology tests. In order to define inconclusive diagnoses, the results suggest the combined use of ELISA+HAI+IFI in 2 blood samples, decreasing the occurrence of false positive/negative results. If results remain inconclusive, the performance of TESA-cruzi and PCR-LIT, if necessary, is recommended.

Dealing with initial inconclusive serological results for chronic Chagas disease in clinical practice

“…Although there was a major concern regarding inconclusive results and the inability to make a correct diagnosis of Chagas disease in the past [12][13][14][15][16], the low prevalence of this problem found in this research reveals that the actual need for nonconventional tests would be low. Nevertheless, reports and guidelines suggested several approaches to deal with inconclusive results or with clinical scenarios where Chagas disease is the most likely diagnosis and serology does not 3,5,14]; the use of WB [5,6,14,15]; the use of PCR [5,6,14]; and other nonconventional tests [3,12,14,16]. From these options, serological follow-up proved to be feasible and appropriate in most cases, and may prove to be a good strategy in places where nonconventional tests are not available.…”

Comparison of conventional serology and PCR methods for the routine diagnosis of Trypanosoma cruzi infection

“…For this reason, all the samples presenting a negative PCR result were repeated twice using a higher DNA concentration, which resulted in a 50% increase in positivity. Picka et al 26 reported that PCR was the technique most likely to resolve inconclusive serology for chagasic infections. PCR also constitutes an excellent tool for T. cruzi detection among transplant or immunosuppressed patients, as antibodies are often absent in these cases.…”

Organ tropism during the acute and chronic phases of Trypanosoma cruzi infection in BALB/c mice

“…This finding demonstrates that the increased sensitivity highlights the importance of including PCR analysis in study protocols to determine the infectivity tension and clarify the inconclusive results for diagnosis of Chagas disease. (4,23,35,36).…”