New human isolates of Trypanosoma cruzi confirm the predominance of hybrid lineages in domestic transmission cycle of the Argentinean Chaco

Macchiaverna, Natalia Paula; Enriquez, Gustavo Fabián; Buscaglia, Carlos A.; Balouz, Virginia; Gürtler, Ricardo E.; Cardinal, Marta Victoria

doi:10.1016/j.meegid.2018.10.001

Cited by 16 publications

(16 citation statements)

References 57 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge, there are few reports of TSSApep-II/V/VI as an antigen for assay with paired samples from chronic patients. Of pre-treatment samples screened by Chagas Sero K-SeT RDT for TSSApep-V/V/VI infection, 91.5% were positive, confirming that these are the predominant infecting lineages in the region, as previously reported [ 30 , 63 ]. Among the patients who completed chemotherapy, a proportion of Chagas Sero K-SeT RDT positives (43.6%) showed IgG decline post-treatment, by visual assessment of band intensity.…”

Section: Discussionsupporting

confidence: 81%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

View full text Add to dashboard Cite

Background Chagas disease remains a significant public health problem in Latin America. There are only two chemotherapy drugs, nifurtimox and benznidazole, and both may have severe side effects. After complete chemotherapy of acute cases, seropositive diagnosis may revert to negative. However, there are no definitive parasitological or serological biomarkers of cure. Methods Following a pilot study with seven Bolivian migrants to Spain, we tested 71 serum samples from chronic patients (mean age 12.6 years) inhabiting the Argentine Chaco region. Benznidazole chemotherapy (5–8 mg/kg day, twice daily for 60 days) was administered during 2011–2016. Subsequently, pre-and post-chemotherapy serum samples were analysed in pairs by IgG1 and IgG ELISA using two different antigens and Chagas Sero K-SeT rapid diagnostic tests (RDT). Molecular diagnosis by kDNA-PCR was applied to post-treatment samples. Results Pilot data demonstrated IgG1 antibody decline in three of seven patients from Bolivia 1 year post-treatment. All Argentine patients in 2017 (averaging 5 years post-treatment), except one, were positive by conventional serology. All were kDNA-PCR-negative. Most (91.5%) pre-treatment samples were positive by the Chagas Sero K-SeT RDT, confirming the predominance of TcII/V/VI. IgG1 and IgG of Argentine patients showed significant decline in antibody titres post-chemotherapy, with either lysate (IgG, P = 0.0001, IgG1, P = 0.0001) or TcII/V/VI peptide antigen (IgG, P = 0.0001, IgG1, P = 0.0001). IgG1 decline was more discriminative than IgG. Antibody decline after treatment was also detected by the RDT. Incomplete treatment was associated with high IgG1 post-treatment titres against lysate (P = 0.013), as were IgG post-treatment titres to TcII/V/VI peptide (P = 0.0001). High pre-treatment IgG1 with lysate was associated with Qom ethnicity (P = 0.045). No associations were found between gender, age, body mass index and pre- or post-treatment antibody titres. Conclusions We show that following chemotherapy of early chronic Chagas disease, significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure. Graphical abstract We show that following chemotherapy of early chronic Chagas disease, a significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure.

show abstract

Section: Discussionsupporting

confidence: 81%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Additionally, in accordance with the UPGMA results of our study, Macchiaverna and collaborators showed that the sequencing data of the T. cruzi TcMK (mevalonate kinase) gene in clinical samples from chronic patients in Argentina, revealed a low rate of genetic variability within the DTU TcV, and showing apparently two robust subgroups of isolates (39).…”

Section: Trypanosomasupporting

confidence: 89%

Intra-Discrete Typing Unit TcV Genetic Variability of Trypanosoma cruzi in Chronic Chagas' Disease Bolivian Immigrant Patients in Barcelona, Spain

Oliveira

Sulleiro

Silva

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Background:Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain.Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis.Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD.Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD.

show abstract

“…Furthermore, none of the 30 seronegative samples was positive by this RDT, indicating that the RDT has greater sensitivity, as might be expected because the RDTs employ higher serum concentrations. Using the observed sensitivity and specificity we estimated that the prevalence of infection with TcII/V/VI in the seropositive human population of Pampa del Indio is 88.2% (95% CI: 76.4–99.0%), which provides further support for the prevalence of hybrid lineages in infected humans from the Chaco, as indicated by time-consuming artificial xenodiagnosis, in vitro culture, parasite isolation and PCR-based lineage identification [35].…”

Section: Discussionmentioning

confidence: 99%

“…Trypanosoma cruzi lineage was determined by PCR of the genomic targets spliced-leader (SL) DNA, 24Sα ribosomal RNA genes and A10 from T. cruzi isolates [32, 33]. For humans only, a second PCR-based protocol targeting two nuclear genes (TcSC5D and TcMK) [34] was also employed [35] to allow for classification of lineages TcI-TcVI as well as TcBat and TcV/VI [34].…”

Section: Methodsmentioning

confidence: 99%

Lineage-specific rapid diagnostic tests can resolve Trypanosoma cruzi TcII/V/VI ecological and epidemiological associations in the Argentine Chaco

et al. 2019

View full text Add to dashboard Cite

Background Trypanosoma cruzi, the protozoan agent of Chagas disease, is comprised of at least 6 genetic lineages (TcI-TcVI). Their geographical distribution, clinical associations and reservoir hosts are not fully elucidated, as genotyping is hampered due to the difficulty in isolating representative populations of organisms. Lineage-specific serological techniques may address these issues. Methods Trypanosoma cruzi lineage-specific serological assays were performed on human, canine, feline and armadillo sera from the Gran Chaco in northern Argentina, a region of ongoing transmission. Synthetic peptides representing lineage-specific epitopes of the trypomastigote small surface antigen (TSSA) were used in ELISA, and the TcII/V/VI shared epitope peptide (TSSApep-II/V/VI) was used in the Chagas Sero K-SeT rapid diagnostic test (RDT). Results Chagas Sero K-SeT RDT, using Protein G to detect human and canine IgG, was at least as sensitive as TSSApep-II/V/VI ELISA using specific secondary antibodies. For sera from humans TSSApep-II/V/VI seroprevalence by Chagas Sero K-SeT was 273/393 (69.5%), for dogs 48/73 (65.8%) and for armadillos 1/7 (14.3%); by ELISA for cats 5/19 (26.3%). The seroprevalence for humans was similar to that for Bolivian patients, amongst whom we previously observed an association of TSSApep-II/V/VI seropositivity with severity of cardiomyopathy. In humans, prevalence of TSSApep-II/V/VI recognition was associated with locality, and with increasing and decreasing age within the Qom and Creole populations, respectively. For dogs TSSApep-II/V/VI recognition was associated with being born before community-wide insecticide spraying (P = 0.05) and with Qom household (P < 0.001). Conclusions We show here that Chagas Sero K-SeT RDT can replace ELISA for TSSApep-II/V/VI serology of humans and dogs; for humans there were statistically significant associations between a positive Chagas Sero K-SeT RDT and being resident in Area IV, and for dogs association with Qom household or with being born before the mass spraying campaign; we also show that with cats the TcII/V/VI epitope can be detected by ELISA. We assessed the lineage distribution in an unprecedented 83% of the human T. cruzi-seropositive population. These results form the basis for more detailed studies, enabling rapid in-the-field surveillance of the distribution and clustering of these lineages among humans and mammalian reservoirs of T. cruzi infection.

show abstract

New human isolates of Trypanosoma cruzi confirm the predominance of hybrid lineages in domestic transmission cycle of the Argentinean Chaco

Cited by 16 publications

References 57 publications

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Intra-Discrete Typing Unit TcV Genetic Variability of Trypanosoma cruzi in Chronic Chagas' Disease Bolivian Immigrant Patients in Barcelona, Spain

Lineage-specific rapid diagnostic tests can resolve Trypanosoma cruzi TcII/V/VI ecological and epidemiological associations in the Argentine Chaco

Contact Info

Product

Resources

About