Efficacy of the Benznidazole+Posaconazole combination therapy in parasitemia reduction: An experimental murine model of acute Chagas.

INTRODUCTION: Benznidazole (BZL) and Nifurtimox (NFX) are the pharmacological treatment for acute phase Chagas Disease (CD); however, therapy resistance and residual mortality development remain important unresolved issues. Posaconazole (POS) has shown a trypanocidal effect in vivo and in vitro. Thus, this study aimed at comparing the T. Cruzi parasitic load-reducing effect of the combination of BZL+POS against that of monotherapy with either, during acute phase CD, in an experimental murine model. METHODS: Nineteen Wistar rats were randomly allocated to four groups and inoculated with the trypomastigotes of T. cruzi strain´s JChVcl1. The rats were administered anti-parasites from day 20-29 post-infection. The Pizzi and Brener method was used for parasitemia measurement. Longitudinal data analysis for the continuous outcome of repeated measures was performed using parasitemia as the outcome measured at days 20, 22, 24, 27, and 29 post-infection. RESULTS: All four groups had similar parasitic loads (p=0.143) prior to therapy initiation. Among the three treatment groups, the BZL+POS (n=5) group showed the highest mean parasitic load reduction (p=0.000) compared with the control group. Likewise, the BZL+POS group rats showed an earlier therapeutic effect and were the only ones without parasites in their myocardial samples. CONCLUSIONS: Treatment of acute phase CD with BZL+POS was more efficacious at parasitemia and myocardial injury reduction, compared with monotherapy with either.

Efficacy of the Benznidazole+Posaconazole combination therapy in parasitemia reduction: An experimental murine model of acute Chagas

Abstract INTRODUCTION: Benznidazole (BZL) and Nifurtimox (NFX) are the pharmacological treatment for acute phase Chagas Disease (CD); however, therapy resistance and residual mortality development remain important unresolved issues. Posaconazole (POS) has shown a trypanocidal effect in vivo and in vitro. Thus, this study aimed at comparing the T. Cruzi parasitic load-reducing effect of the combination of BZL+POS against that of monotherapy with either, during acute phase CD, in an experimental murine model. METHODS Nineteen Wistar rats were randomly allocated to four groups and inoculated with the trypomastigotes of T. cruzi strain´s JChVcl1. The rats were administered anti-parasites from day 20-29 post-infection. The Pizzi and Brener method was used for parasitemia measurement. Longitudinal data analysis for the continuous outcome of repeated measures was performed using parasitemia as the outcome measured at days 20, 22, 24, 27, and 29 post-infection. RESULTS All four groups had similar parasitic loads (p=0.143) prior to therapy initiation. Among the three treatment groups, the BZL+POS (n=5) group showed the highest mean parasitic load reduction (p=0.000) compared with the control group. Likewise, the BZL+POS group rats showed an earlier therapeutic effect and were the only ones without parasites in their myocardial samples. CONCLUSIONS: Treatment of acute phase CD with BZL+POS was more efficacious at parasitemia and myocardial injury reduction, compared with monotherapy with either.

SNP/haplotype associations of CCR2 and CCR5 genes with severity of chagasic cardiomyopathy.

BACKGROUND: Chronic inflammation plays a major role in the tissue injury seen in the chronic chagasic cardiomyopathy. The CCR2 and CCR5 chemokine receptors are involved with the type of cellular infiltrate present in cardiac tissue and CCR5-gene variants were previously associated with this pathology. METHODS AND RESULTS: This is a replication study in an independent cohort with larger sample size. Nine SNPs of CCR5 and CCR2 were typified to confirm the association previously found with Chagas disease. Evidence of association with severity was found for the A allele of rs1799864 of CCR2 (pad=0.02; OR=1.91, 95% CI=1.10-3.30), the T allele of the rs1800024 of CCR5 (pad=0.01; OR=1.95, 95% CI=1.13-3.38), and the HHF(∗)2 haplotype (p=0.03, OR=1.65, 95% CI=1.03-2.65). These results were replicated in the study combined with previous data. In this analysis it was replicated the allele T of rs2734648 (pad=0.009, OR=0.52, 95% CI=0.32-0.85) with protection. In addition, the allele G of rs1800023 (pad=0.043, OR=0.61, 95% CI=0.38-0.98), and the HHC haplotype (p=0.004, OR=0.62, 95% CI=0.44-0.86) were also associated with protection. In contrast, the allele A of rs1799864 of CCR2 (pad=0.009; OR=1.90, 95% CI=1.17-3.08); and the allele T of rs1800024 of CCR5 (pad=0.005, OR=1.98, 95% CI=1.22-3.23) were associated with greater severity. No evidence of association between symptomatic and asymptomatic patients was observed. CONCLUSIONS: These results confirm that variants of CCR5 and CCR2 genes and their haplotypes are associated with the severity but not with susceptibility to develop chagasic cardiomyopathy.

Endocarditis infecciosa de alto riesgo embolígeno durante el embarazo: ¿manejo conservador o quirúrgico? / High risk infective endocarditis embolism during pregnancy: Medical or surgical management?

Presentamos el caso de una paciente de 22 años de edad con embarazo de 14 semanas y endocarditis infecciosa de válvula mitral nativa con una vegetación de 15 mm con amplia movilidad, acompañada de insuficiencia valvular severa. Inicialmente, y pese al riesgo embolígeno, se dio tratamiento antibiótico durante 4 semanas. Por persistencia del tamaño de la vegetación se decide llevar a cirugía para reparación mitral y remoción de la lesión en la semana 18 de gestación, considerando que el balance entre el riesgo fetal y materno estaba a favor del procedimiento quirúrgico. Se usaron técnicas de protección fetal intraoperatoria y se colocó una prótesis biológica previo intento de reparación. La evolución postintervención fue satisfactoria, lográndose parto por cesárea a las 30 semanas.

A 22-year-old pregnant woman was seen at 14 weeks of pregnancy for infective endocarditis with a vegetation of 15 mm and wide mobility, which affected the native mitral valve accompanied by severe valvular insufficiency. Antibiotic treatment was given for 4 weeks despite the embolism risk. Due to persistence of vegetation size and after considering the fetal and maternal risk, the surgical procedure was favored. We decided to perform valvuloplasty and removal of lesion at 18 weeks of pregnancy. Fetal protection techniques were used and a bioprosthesis was placed before attempting a repair. The postoperative follow-up was satisfactory, achieving a successful birth by cesarean section at 30 weeks.

[High risk infective endocarditis embolism during pregnancy: Medical or surgical management?]. / Endocarditis infecciosa de alto riesgo embolígeno durante el embarazo: ¿manejo conservador o quirúrgico?

A 22-year-old pregnant woman was seen at 14 weeks of pregnancy for infective endocarditis with a vegetation of 15 mm and wide mobility, which affected the native mitral valve accompanied by severe valvular insufficiency. Antibiotic treatment was given for 4 weeks despite the embolism risk. Due to persistence of vegetation size and after considering the fetal and maternal risk, the surgical procedure was favored. We decided to perform valvuloplasty and removal of lesion at 18 weeks of pregnancy. Fetal protection techniques were used and a bioprosthesis was placed before attempting a repair. The postoperative follow-up was satisfactory, achieving a successful birth by cesarean section at 30 weeks.