Interleukin 10 Polymorphisms as Risk Factors for Progression to Chagas Disease Cardiomyopathy: A Case-Control Study and Meta-Analysis.

Background: Chagas disease is a lifelong infection caused by the protozoa Trypanosoma cruzi endemic in Latin-America and emergent worldwide. Decades after primary infection, 20-30% of infected people develop chronic Chagas cardiomyopathy (CCC) while the others remain asymptomatic. CCC pathogenesis is complex but associated with sustained pro-inflammatory response leading to tissue damage. Hence, levels of IL-10 could have a determinant role in CCC etiology. Studies with Latin-American populations have addressed the association of genetic variants of IL-10 and the risk of developing CCC with inconsistent results. We carried out a case control study to explore the association between IL-10-1082G>A (rs18008969), -819C>T (rs1800871), -592A>C (rs1800872) polymorphisms and CCC in a population attending a hospital in Buenos Aires Argentina. Next, a systematic review of the literature and a meta-analysis were conducted combining present and previous studies to further study this association. Methods: Our case control study included 122 individuals with chronic T. cruzi infection including 64 patients with any degree of CCC and 58 asymptomatic individuals. Genotyping of IL-10 -1082G>A, -819C>T, -592A>C polymorphisms was performed by capillary sequencing of the region spanning the three polymorphic sites and univariate and multivariate statistical analysis was undertaken. Databases in English, Spanish and Portuguese language were searched for papers related to these polymorphisms and Chagas disease up to December 2021. A metanalysis of the selected literature and our study was performed based on the random effect model. Results: In our cohort, we found a significant association between TT genotype of -819 rs1800871 and AA genotype of -592 rs1800872 with CCC under the codominant (OR=5.00; 95%CI=1.12-23.87 P=0,04) and the recessive models (OR=5.37; 95%CI=1.12-25.68; P=0,03). Of the genotypes conformed by the three polymorphic positions, the homozygous genotype ATA was significantly associated with increased risk of CCC. The results of the meta-analysis of 754 cases and 385 controls showed that the TT genotype of -819C>T was associated with increased CCC risk according to the dominant model (OR=1.13; 95% CI=1.02-1.25; P=0,03). Conclusion: The genotype TT at -819 rs1800871 contributes to the genetic susceptibility to CCC making this polymorphism a suitable candidate to be included in a panel of predictive biomarkers of disease progression.

Molecular typing of Strongyloides stercoralis in Latin America, the clinical connection.

This study analysed Strongyloides stercoralis genetic variability based on a 404 bp region of the cox1 gene from Latin-American samples in a clinical context including epidemiological, diagnosis and follow-up variables. A prospective, descriptive, observational study was conducted to evaluate clinical and parasitological evolution after ivermectin treatment of 41 patients infected with S. stercoralis. Reactivation of the disease was defined both by clinical symptoms appearance and/or direct larvae detection 30 days after treatment or later. We described 10 haplotypes organized in two clusters. Most frequent variants were also described in the Asian continent in human (HP24 and HP93) and canine (HP24) samples. Clinical presentation (intestinal, severe, cutaneous and asymptomatic), immunological status and eosinophil count were not associated with specific haplotypes or clusters. Nevertheless, presence of cluster 1 haplotypes during diagnosis increased the risk of reactivation with an odds ratio (OR) of 7.51 [confidence interval (CI) 95% 1.38­44.29, P = 0.026]. In contrast, reactivation probability was 83 times lower if cluster 2 (I152V mutation) was detected (OR = 0.17, CI 95% 0.02­0.80, P = 0.02). This is the first analysis of S. stercoralis cox1 diversity in the clinical context. Determination of clusters during the diagnosis could facilitate and improve the design of follow-up strategies to prevent severe reactivations of this chronic disease.