Complexos imínicos de cobre com atividade antiparasitária frente à doença de chagas / Imine copper complexes with antiparasitic activity against Chagas disease

Neste trabalho foram sintetizados e caracterizados três complexos de cobre com ligantes imínicos, com o objetivo de avaliar sua atividade tripanocida. Esses complexos foram caracterizados por diversas técnicas espectroscópicas, como UV-Vis, Infravermelho e EPR, além de análise elementar e espectrometria de massa. Juntamente com outros complexos similares previamente sintetizados pelo nosso grupo, tiveram suas atividades avaliadas frente à forma tripomastigota do parasita T. cruzi, responsável pela fase aguda da doença de Chagas, por ensaios de viabilidade celular, com determinação do valor de seus IC50, concentração em que observamos a morte de 50% da cultura celular, pela metodologia denominada MTT. Todos os complexos mostraram-se eficientes frente a tripomastigotas, apresentando valores de IC50 abaixo de 10 µM, com quatro deles obtendo índice de seletividade maior que 10, fator importante para definir agentes promissores antichagásicos. Complexos selecionados também tiveram sua atividade verificada frente à forma amastigota do parasita, responsável pela fase crônica da doença, utilizando método de imageamento por microscópio de fluorescência e contagem celular. Estudos de inibição da cruzaína, uma cisteíno-protease importante para o metabolismo do parasita foram conduzidos em colaboração com o laboratório do Prof. Wagner Alves de Souza Júdice, da Universidade de Mogi das Cruzes. Quatro dos compostos testados apresentaram atividade inibitória frente a cruzaína, sendo dois de cobre, um de zinco e um ligante livre. Os estudos também permitiram diferenciar os mecanismos de inibição dos compostos, com os complexos de cobre apresentando um mecanismo de inibição clássico e o composto de zinco e o ligante livre apresentando o mecanismo de inibição competitiva parabólica com cooperatividade

In this work, three copper complexes with iminic ligands were synthesized and characterized, with the objective of evaluating their trypanocidal activity. These complexes were characterized by several spectroscopic techniques, such as UV-Vis, Infrared and EPR, in addition to elementary analysis and mass spectrometry. Together with other similar complexes previously synthesized by our group, their activities were evaluated against the trypomastigote form of the parasite T. cruzi, responsible for the acute phase of Chagas disease, by cell viability tests, with determination of the value of their IC50, concentration in that we observed the death of 50% of the cell culture, by the methodology called MTT, all presenting IC50 values below 10 µM, with four of them obtaining a selectivity index greater than 10, important factor for defining promising antichagasic agents. Selected complexes also had their activity verified against the amastigote form of the parasite, responsible for the chronic phase of the disease, using a fluorescence microscope and cell counting imaging method. Inhibition studies of cruzain, a cysteine protease important for the metabolism of the parasite, were conducted in collaboration with the laboratory of Professor Wagner Alves de Souza Júdice at the University of Mogi das Cruzes. Four of the tested compounds showed inhibitory activity against cruzain, two of copper, one of zinc and a free ligand. The studies also allowed to differentiate the mechanisms of inhibition of the compounds, with the copper complexes presenting a classic inhibition mechanism and the zinc compound and the free ligand presenting the competitive parabolic inhibition mechanism with cooperativity

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.

Response to different benznidazole doses in animal models of chronic phase Chagas disease: a critical review

Abstract Chagas disease is a protozoan infection that was identified over a century ago. No drugs are available to treat the indeterminate and determinate chronic phases of the disease. Success of a drug design is dependent on correct biological evaluation. Concerning new drug designs for Chagas disease, it is essential to first identify the most effective, existing, experimental chronic protocols that can be used for comparison purposes. Here, we present a literature review regarding experimental models with chronic Chagas disease to evaluate the efficacy of benznidazole (BZN). We searched literature published in PubMed and Web of Science databases, using these keywords: animal model, BZN, Chagas disease, T. cruzi, and chronic phase, with no timeframe limitations. We excluded articles involving acute phase animal models and/or those without BZN treatment. The selected studies were conducted using different BZN concentrations (10mg-100mg) involving several different periods (5-70 days). Concentrations and durations of use are directly related to side effects, but do not prevent chronic tissue lesions. BZN use during the late/chronic phases of Chagas disease is unable to eliminate amastigote forms present in infected tissues. This study suggests the administration of a lower BZN concentration (<100mg/kg/day) during the chronic phase of the animal model, as this had been reported to result in fewer side effects.

Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination

Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.

Benznidazole therapy for Chagas disease in asymptomatic Trypanosoma cruzi -seropositive former blood donors: evaluation of the efficacy of different treatment regimens

Abstract: INTRODUCTION: Chagas disease currently affects 5.7 million people in Latin America and is emerging in non-endemic countries. There is no consensus concerning the efficacy of trypanocidal therapy for patients with the chronic form of the disease. We evaluated cardiac function and sociodemographic, clinical, and serologic characteristics of a group of asymptomatic Trypanosoma cruzi-seropositive former blood donors, and compared the effects of benznidazole treatment applied for different lengths of time. METHODS: Blood donors who screened positive for T. cruzi between 1998 and 2002 were recruited 10 years later for follow-up (n = 244); 46 individuals had received treatment. Three subjects had terminated treatment prematurely. The remaining 43 individuals were divided into two groups: individuals who had received benznidazole therapy for 50-60 days (n = 28; BT ≤60 group) or more than 60 days (n = 15; BT >60). Serologic assays, biochemical tests, electrocardiographic, echocardiographic, and clinical examinations were performed on all participants. Parasite loads were determined by qualitative and quantitative polymerase chain reaction. RESULTS: Parasitemia was significantly reduced in the BT ≤60 and BT >60 groups compared with the untreated group. There were no differences in epidemiologic profiles or clinical, biochemical, electrocardiographic, or echocardiographic data between any of the groups. CONCLUSIONS: Despite elimination or significant reduction in parasitemia in patients with chronic Chagas disease who received benznidazole, there was no clinical difference between those who were treated for >60 days and those treated for a shorter duration. Furthermore, the adverse effects of benznidazole appear to be less severe than previous reports would suggest.

Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole

Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective.

Long-term follow-up of a patient since the acute phase of Chagas disease (South American trypanosomiasis): further treatment and cure of the infection

ABSTRACTA woman had been followed since 1957 for acute phase Chagas disease. Parasitological and serological tests were positive, and treatment included benznidazole in 1974. Following treatment, parasitological test results were negative and conventional serology remained positive until 1994, with subsequent discordant results (1995-1997). The results became consistently negative since 1999. She had an indeterminate chronic form until 1974. Only two minor and transitory nonspecific alterations on electrocardiogram were noted, with the last nine records normal until June 2014. This case confirms the possibility of curing chronic disease and suggests the benefit of specific treatments for preventing long-term morbidity.

Avaliação das quimiocinas e da expressão de seus receptores em células mononucleares de pacientes portadores da doença de Chagas submetidas à infecção in vitro com Trypanosoma cruzi e tratamento com benzonidazol / Evaluation of chemokines and their receptors expression in patient mononuclear patients of Chagas disease undergoing in vitro infection with Trypanosoma cruzi and treatment with benznidazole

Atualmente o Brasil apresenta 3 milhões de indivíduos portadores da cardiomiopatia chagásica. Porém, tratamento etiológico com o fármaco Benzonidazol (BZ) na fase crônica da doença ainda não está elucidado. Acredita-se que a recomendação do BZ nessa fase, pode prevenir ou retardar a evolução clínica da cardiomiopatia na Doença Chagas (DC). Assim o objetivo do estudo é avaliar a produção de quimiocinas e expressão de seus receptores em Células mononucleares do sangue periférico - PBMC (de portadores crônicos da doença de Chagas) submetidas in vitro ao tratamento com BZ, após a infecção com T.cruzi. Foram selecionados 11 pacientes na fase crônica da doença. Amostras de sangue desses pacientes foram coletadas para obtenção de PBMC, em que foram cultivadas em placas de cultivo na concentração de 106 células/ml por poço. Após a adesão das células aderentes (principalmente macrófagos), as células não aderentes (principalmente linfócitos) foram removidas e as formas tripomastigotas foram adicionadas ao cultivo para infecção das células aderentes. Subsequente a incubação, as células não aderentes foram adicionadas novamente ao cultivo juntamente com o fármaco Bz (1µg/mL), ficando um co-cultivo de células aderentes infectadas com T.cruzi, células não aderentes e o BZ (C+T+BZ). As placas de cultura foram incubadas por períodos de 24h e 5 dias. Para uma análise fidedigna da ação do BZ nas células aderentes e não aderentes foi necessário a criação dos controles: células (C), células e tripomastigotas (C+T) e células e o BZ (C+BZ). Após o cultivo, foram coletados os sobrenadantes das culturas, para avaliação da produção de quimiocinas (CCL2, CXL9, CXL10, CCL5 e CXCL8) por CBA (Cytometric Bead Array). Posteriormente foi realizada a imunofenotipagem...

Chronic phase of Chagas disease: why should it be treated? A comprehensive review

The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i) repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii) combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.

Reações adversas em pacientes com doença de Chagas tratados com benzonidazol, no Estado do Ceará / Adverse reactions in Chagas disease patients treated with benznidazole, in the State of Ceará

INTRODUÇÃO: A doença de Chagas, causada pelo Trypanosoma cruzi, é tratada com benzonidazol, tendo o inconveniente de apresentar efetividade parcial e alta toxicidade, que varia desde reações de hipersensibilidade a aplasia medular. O objetivo foi descrever e avaliar a ocorrência de reações adversas em pacientes chagásicos em tratamento com benzonidazol em Fortaleza, Ceará. MÉTODOS: Estudo descritivo prospectivo envolvendo 32 pacientes chagásicos crônicos tratados com benzonidazol entre janeiro de 2005 e abril de 2006. Dados sociodemográficos e clínicos foram coletados de questionários, entrevistas e exames laboratoriais. As amostras de sangue foram coletadas antes, com 30 e 60 dias de tratamento. RESULTADOS: Reações adversas foram relatadas em 28 (87,5 por cento) pacientes tratados, tendo sido as mais frequentes: prurido (50 por cento), formigamento (43,8 por cento), fraqueza muscular (37,5 por cento) e rash cutânea (31,3 por cento). Dos 28 pacientes com reações adversas, oito (28,57 por cento) interromperam o tratamento. Reações adversas que culminaram com a suspensão do tratamento foram formigamento sete (87,5 por cento) ou erupção cutânea cinco (62,5 por cento). Observou-se aumento discreto dos níveis de aminotransferases durante o tratamento em (9,4 por cento) pacientes. CONCLUSÕES: Concluindo, o acompanhamento farmacoterapêutico dos pacientes chagásicos é de grande relevância na prevenção e detecção precoce das reações adversas a medicamentos.

INTRODUCTION: Chagas disease is caused by Trypanosoma cruzi and treated with benznidazole (BNZ). This drug has the troublesome features of presenting partial effectiveness and high toxicity ranging from hypersensitivity reactions to medullary aplasia. The objective here was to describe and evaluate the occurrence of adverse reactions in Chagas disease patients treated with benznidazole in Fortaleza, Ceará. METHODS: This was a prospective descriptive study involving 32 chronic Chagas patients treated with benznidazole between January 2005 and April 2006. Sociodemographic and clinical data were collected through questionnaires, interviews and laboratory tests. Blood samples were collected before treatment and after 30 and 60 days of treatment. RESULTS: Adverse reactions were reported in 28 patients (87.5 percent) patients and the most frequent of these were pruritus (50 percent), prickling (43.8 percent), muscle weakness (37.5 percent) and skin rash (31.3 percent). Out of the 28 patients with adverse reactions, eight (28.57 percent) discontinued their treatment. The adverse reactions that culminated with discontinuation of the treatment were prickling (7; 87.5 percent) or skin eruptions (5; 62.5 percent). There was a slight increase in aminotransferase levels during the treatment in 9.4 percent of the patients. CONCLUSIONS: Following up the drug therapy administered to Chagas patients is of great importance for prevention and early detection of adverse reactions to drugs.

The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease

Among the pathophysiological derangements operating in the chronic phase of Chagas disease, parasite persistence is likely to constitute the main mechanism of myocardial injury in patients with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless, inflammatory process and induces myocardial autoimmune injury. These facts suggest that trypanocidal therapy may positively impact the clinical course of patients with chronic Chagas heart disease. However, the experimental and clinical evidence currently available is insufficient to support the routine use of etiologic treatment in these patients. The BENEFIT project - Benznidazole Evaluation for Interrupting Trypanosomiasis - is an international, multicenter, double-blind, placebo-controlled trial of trypanocidal treatment with benznidazole in patients with chronic Chagas heart disease. This project is actually comprised of two studies. The pilot study investigates whether etiologic treatment significantly reduces parasite burden, as assessed by polymerase chain reaction-based techniques and also determines the safety and tolerability profile of the trypanocidal drug in this type of chagasic population. The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease.

Present situation and new strategies for Chagas disease chemotherapy: a proposal

Treatments for Chagas disease have been administered since the first attempts by Mayer & Rocha Lima (1912, 1914) and up to the drugs currently in use (nifurtimox and benznidazole), along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles), in separate form. Several diseases such as tuberculosis, leprosy and AIDS only came under control after they were treated with associations of drugs with different mechanisms of action. This not only boosts the action of the different compounds, but also may avoid the development of parasite resistance .To this end, over the short term, we propose experimental studies on laboratory animals and clinical trials with the following associations: (i) nifurtimox (8 mg/kg/day) + benznidazole (5 mg/kg/day) x 60 consecutive days; (ii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + allopurinol (8-10 mg/kg/day) x 60 days and (iii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + ketoconazole, fluconazole or itraconazole (5-6 mg/kg/day) x 60 consecutive days. The doses of the drugs and the treatment schedules for the clinical trials must be adapted according to the side effects. From these, other double or triple associations could be made, using drugs with different mechanisms of action. This proposal does not exclude investigations on new drugs over the median and long terms, targeting other aspects of the metabolism of Trypanosoma cruzi. Until such time as the ideal drug for specific treatment of Chagas disease might be discovered, we need to develop new strategies for achieving greater efficacy with the old drugs in associations and to develop rational experimentation with new drugs.

Aspectos clínicos, epidemiológicos e patológicos da infecção natural em bovinos por Trypanosoma vivax na Paraíba / Clinical, epidemiological and pathological signs of natural infection in cattle by Trypanosoma vivax in Paraíba, Brazil

Descrevem-se dois surtos de tripanossomíase por Trypanosoma vivax em bovinos, ocorridos em dois estabelecimentos do alto sertão da Paraíba. Os sinais clínicos, a patologia e a epidemiologia da doença foram estudados no período de maio de 2005 a novembro de 2006.T. vivax foi identificado em esfregaços da capa leucocitária e mediante a reação em cadeia da polimerase (PCR). Os animais afetados apresentaram anorexia, depressão, febre, anemia, perda de peso, redução da produção leiteira, cegueira transitória, aborto e sinais nervosos caracterizados por incoordenação motora, salivação, opistótono, nistagno, tetania e bruxismo. Todos os animais que apresentaram sintomatologia nervosa morreram. As alterações macroscópicas observadas em um bovino submetido à necropsia foram aumento de volume dos linfonodos, atrofia serosa dos depósitos de gordura, aumento de volume do baço com evidência da polpa branca, hidropericárdio, além de petéquias e equimoses no epicárdio. Histologicamente havia meningoencefalite. O controle da doença na propriedade com tratamento específico dos casos clínicos com aceturato de diminazene foi eficiente, pois após o tratamento não se verificou mais a presença do parasita em esfregaços sanguíneos nem evidência clínica da enfermidade em até 2 meses após o início do surto. Os fatores epidemiológicos favoráveis à ocorrência dos surtos foram a abundância de vetores mecânicos, como tabanídeos e Stomozys spp., e a entrada, no rebanho, de animais oriundos de propriedades onde ocorreu a doença em questão. Sugere-se que o semi-árido do Nordeste, devido a períodos prolongados de secas e altas temperaturas, é região de instabilidade enzoótica para a tripanossomíase, em conseqüência, provavelmente, ao ambiente desfavorável para o desenvolvimento de vetores durante a maior parte do ano.

Two outbreaks of trypanosomiasis by Trypanosoma vivax, reported in cattle, occurred on two farms located in the state of Paraíba, northeastern Brazil. The epidemiology, clinical signs and pathology of the disease were studied from May 2005 to November 2006. T. vivax was identified morphologically and by polymerase chain reaction test (PCR). The affected cattle presented anorexia, depression, fever, anemia, weight loss, reduction in milk production, transitory blindness, abortion and some nervous signs as nystagmus, tetany and bruxism. All cattle that presented nervous signs died. Necropsy findings were enlarged lymph and spleen, serous atrophy of the fat depots, proeminence of the splenic white pulp, hydropericardium and pericardial petechiae and ecchymoses on the epicardium. Histologically there was meningoencephalitis. The treatment of the clinical cases with diminazena aceturate was efficient with clearance of the parasite from the blood or disappearance of clinical signs in up to 2 months after the beginning of the outbreak on the two farms studied. The epidemiologic factors favoring the occurrence of the outbreak were the abundance of mechanical vectors, as tabanids and Stomoxys sp., and the introduction into the herd of cattle from farms where the disease occurred. It is suggested that the semiarid of the Brazilian Northeast is an enzootic instability region for trypanosomiasis due to its prolonged periods of drought and high temperatures, constituting during most part of the year an unfavorable environment for the development of vectors.

Benznidazole vs benznidazole in multilamellar liposomes: how different they interact with blood components?

In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZÎs association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45 percent and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 ± 20 vs 102 ± 15 ml/kg) and total clearance (35.23 ± 2.3 vs 21.9 ± 1.4 ml/h.kg), and lower concentration-time curve (7.23 ± 0.2 vs 9.16 ± 0.5 æg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70 percent, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected.

Tratamiento de la enfermedad de Chagas con benznidazol y acido tioctico / Treatment of chagas disease with benznidazole and thioctic acid

Se realizó un ensayo clínico controlado, multicéntrico, a triple ciego, para evaluar si el tratamiento oral combinado del ácido tióctico (AT), reduce la incidencia de los efectos secundarios asociados al tratamiento con benznidazol (BZ) en pacientes infectados con Trypanosoma cruzi. Cuatro esquemas fueron asignados al azar pareados por edad, administrando placebo o AT por vía oral a razón de 50-100 mg día a dosis e intervalos variables (con y sin período pre-inducción) en combinación con BZ a dosis de 5 mg/kg/día por 30 días. Se realizaron evaluaciones en los días 10, 20, 37 y 52 de iniciado el tratamiento. Fueron enrolados 249 pacientes con edades entre 15 y 44 años. El 70.3% de los pacientes completó el tratamiento y el 17.7% restante debió suspender la medicación por causas relacionadas al BZ. La proporción de personas afectadas por al menos un efecto adverso, fue semejante entre los 4 grupos: entre 54.8 y 58%, aunque en ninguno de ellos resultó de carácter grave. Las manifestaciones clínicas adversas fueron: exantema morbiliforme (28%); prurito (13.6%); cefalea (8%); epigastralgia (6.2%); fiebre (6.2%); astenia (4.3%); náuseas (4.0%); mialgias (4.3%); vómitos (3.2%); otros (21.5%). La incidencia de experiencias adversas no difirió significativamente entre los 4 esquemas terapéuticos, ni entre los diferentes intervalos de edad de los pacientes. La asociación con ácido tióctico no demostró prevenir las manifestaciones de intolerancia a este agente. No obstante, la administración de BZ en un ciclo mensual único a pacientes infectados logró una elevada tasa de adherencia al tratamiento ambulatorio.

Enfermedad de Chagas-Mazza congenita en Salta / Congenital Chagas-Mazza disease in Salta, Argentina

Se estudió la infección por T. cruzi en mujeres embarazadas en la localidad de General Güemes, provincia de Salta. La misma fue del 12,3 por cento. El 8,8 por cento de los recién nacidos estudiados tuvieron diagnóstico de Enfermedad de Chagas utilizando la técnica directa (microhematocrito). Todos fueron tratados con benznidazol a razón de 5mg/kg/día durante 30 dias. Todos presentaron anemia, que fue interpretada como reacción adversa medicamentosa. Se estima que la técnica directa representa la mejor opción para llevar a cabo el diagnóstico de esta enfermedad en el recién nacido. Se ha propuesto un flujograma para el seguimiento de la infección por T. cruzi en el recién nacido