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.

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.

Polymorphisms of toll-like receptor 2 and 4 genes in Chagas disease

The aim of this study was to test the possible implication of toll-like receptor 2 (TLR2) and TLR4 gene polymorphisms in determining the susceptibility to Chagas' disease. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 475 individuals from Colombia, 143 seropositive with chagasic cardiomyopathy, 132 seropositive asymptomatic and 200 seronegative. The TLR2 arginine to glutamine substitution at residue 753(Arg753Gln) polymorphism was absent in the groups analyzed. The TLR4 Asp299Gly and Thr399Ile polymorphisms are in linkage disequilibrium and we observed a very low frequency of these polymorphisms in our study population (2.6 percent and 1.8 percent respectively). The overall TLR2 and TLR4 alleles and genotype distribution in seronegative and seropositive were not significantly different. We compared the frequencies between asymptomatic patients and those with chagasic cardiomyopathy and we did not observe any significant differences in the distribution of alleles or genotypes. In summary, this study corroborates the low frequency of TLR2 and TLR4 polymorphisms observed in other populations and suggest that these do not play an important role in Chagas' disease. The validation of these findings in independent cohorts is needed to firmly establish a role for TLR2 and TLR4 variants in Chagas' disease.