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Mem. Inst. Oswaldo Cruz ; 115: e190389, 2020. tab, graf
Article in English | LILACS | ID: biblio-1091236


BACKGROUND Chagas disease, which is caused by the protozoan Trypanosoma cruzi, is endemic to Latin America and mainly affects low-income populations. Chemotherapy is based on two nitrocompounds, but their reduced efficacy encourages the continuous search for alternative drugs. Our group has characterised the trypanocidal effect of naphthoquinones and their derivatives, with naphthoimidazoles derived from β-lapachone (N1, N2 and N3) being the most active in vitro. OBJECTIVES In the present work, the effects of N1, N2 and N3 on acutely infected mice were investigated. METHODS in vivo activity of the compounds was assessed by parasitological, biochemical, histopathological, immunophenotypical, electrocardiographic (ECG) and behavioral analyses. FINDINGS Naphthoimidazoles led to a decrease in parasitaemia (8 dpi) by reducing the number of bloodstream trypomastigotes by 25-50% but not by reducing mortality. N1 protected mice from heart injury (15 dpi) by decreasing inflammation. Bradycardia was also partially reversed after treatment with N1 and N2. Furthermore, the three compounds did not reverse hepatic and renal lesions or promote the improvement of other evaluated parameters. MAIN CONCLUSION N1 showed moderate trypanocidal and promising immunomodulatory activities, and its use in combination with benznidazole and/or anti-arrhythmic drugs as well as the efficacy of its alternative formulations must be investigated in the near future.

Animals , Male , Mice , Trypanocidal Agents/therapeutic use , Naphthoquinones/therapeutic use , Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Time Factors , Trypanocidal Agents/chemistry , Acute Disease , Naphthoquinones/chemistry , Parasitemia/drug therapy , Disease Models, Animal , Electrocardiography , Anti-Inflammatory Agents , Nitroimidazoles/chemistry
Rev. Soc. Bras. Med. Trop ; 53: e20190443, 2020. tab
Article in English | LILACS | ID: biblio-1101452


Abstract INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Humans , Male , Female , Aged , Chagas Disease/drug therapy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Socioeconomic Factors , Severity of Illness Index , Algorithms , Brazil/epidemiology , Chronic Disease , Middle Aged
Rev. Soc. Bras. Med. Trop ; 53: e20190477, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057272


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.

Animals , Rats , Triazoles/administration & dosage , Trypanocidal Agents/administration & dosage , Chagas Disease/drug therapy , Parasitemia/drug therapy , Nitroimidazoles/administration & dosage , Acute Disease , DNA, Protozoan , Rats, Wistar , Disease Progression , Disease Models, Animal , Drug Therapy, Combination , Parasite Load
Rev. Soc. Bras. Med. Trop ; 53: e20190150, 2020. tab
Article in English | LILACS | ID: biblio-1057268


Abstract INTRODUCTION: Benznidazole is used for treating Chagas disease (CD). This cross-sectional study aimed to characterize the adverse drug reactions (ADRs) of benznidazole at a public hospital in Brazil's Federal District. METHODS: Medical records were analyzed and ADRs were categorized by type, intensity, seriousness, and causality. RESULTS: Of the 62 patients who started benznidazole treatment for CD, 41 (66%) presented with 105 ADRs; 23 (37%) discontinued the treatment. Most reactions were classified as probable (81%), severe (63%), serious (67%), and dose-dependent (56%). CONCLUSIONS: The high incidence of ADRs because of treatment withdrawal revealed the need for safer alternatives for CD treatment.

Humans , Male , Female , Adult , Trypanocidal Agents/adverse effects , Chagas Disease/drug therapy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Nitroimidazoles/adverse effects , Socioeconomic Factors , Trypanocidal Agents/therapeutic use , Severity of Illness Index , Brazil/epidemiology , Hemagglutination Tests , Incidence , Cross-Sectional Studies , Drug-Related Side Effects and Adverse Reactions , Hospitals, Public , Middle Aged , Nitroimidazoles/therapeutic use
Acta bioquím. clín. latinoam ; 53(2): 209-215, jun. 2019. ilus, graf, tab
Article in Spanish | LILACS | ID: biblio-1019255


La enfermedad de Chagas afecta aproximadamente a 10 millones de personas en Sudamérica y 1,5 millones en la Argentina. La transmisión congénita es la más importante en áreas urbanas. Existen dos drogas aprobadas para el tratamiento: nifurtimox (Laboratorios Bayer) y benznidazol (BNZ) (Laboratorios Roche, LAFEPE y Elea) que fueron desarrolladas hace más de 40 años y cuya farmacología y metabolismo en humanos han sido poco estudiados. La información disponible es virtualmente inexistente en niños y mujeres embarazadas. Se busca aportar estudios sistemáticos hacia una farmacoterapéutica racional en niños ya que empíricamente ha demostrado gran efectividad. Se desarrollaron métodos bioanalíticos aplicables a matrices biológicas como plasma, orina y leche materna para las drogas madres y la identificación de metabolitos en muestras de pacientes bajo terapéutica. La farmacocinética poblacional pediátrica descripta aquí para BNZ es concluyente respecto de sus diferencias con la farmacocinética en adultos. Se identificaron tres compuestos presentados como metabolitos del BNZ. La transferencia de dicho fármaco a la leche materna no supone riesgo para el lactante. Estos resultados brindan información para mejorar los protocolos de tratamiento existentes buscando una farmacoterapéutica adaptada a la edad y un uso más seguro de los fármacos en niños y eventualmente en adultos.

Chagas disease affects approximately 10 million people in South America and 1.5 million in Argentina. Congenital transmission is most important in urban areas. There are two drugs approved for treatment: nifurtimox (Bayer) and benznidazole (BNZ) (Roche, LAFEPE, Elea),developed more than 40 years ago. Their pharmacology and metabolism in humans have been seldom studied. The information available on children and pregnant women is virtually non-existent. The aim of this study is to provide systematic studies towards a rational pharmacotherapeutic sin children, which has been empirically proven to be highly effective. Bioanalytical methods were developed for plasma, urine and breast milk for parent drugs and for the identification of their metabolites in samples of patients under treatment. The pediatric population pharmacokinetics described here for BNZ is conclusive about their differences from adult pharmacokinetics. Three compounds presented as BNZ metabolites were identified. The transfer of this drug to the breast milk does not present a risk to the infant. These evidences offer information to improve the existing treatment protocols, seeking a pharmacotherapy adapted to the age and a safer use of the drugs in children and eventually in adults.

A doença de Chagas afeta aproximadamente 10 milhões de pessoas na América do Sul e 1,5 milhão na Argentina. A transmissão congênita é a mais importante em áreas urbanas. Existem dois medicamentos aprovados para o tratamento: nifurtimox (Laboratórios Bayer) e benznidazol (BNZ) (Laboratórios Roche, LAFEPE e Elea), desenvolvidas há mais de 40 anos, e sua farmacologia e seu metabolismo em humanos têm sido pouco estudados. A informação disponível é praticamente inexistente em crianças e mulheres grávidas. O objetivo é fornecer estudos sistemáticos para uma farmacoterapêutica racional em crianças visto que foram comprovadas empiricamente como sendo altamente eficazes. Métodos bioanalíticos aplicáveis a matrizes biológicas como plasma, urina e leite materno para fármacos-mãe e para a identificação de metabólitos em amostras de pacientes em tratamento terapêutico foram desenvolvidos. A farmacocinética da população pediátrica aqui descrita para BNZ é conclusiva em relação às suas diferenças com a farmacocinética de adultos. Três compostos apresentados como metabólitos do BNZ foram identificados. A transferência do referido medicamento para o leite materno não representa risco para o lactente. Essas evidências oferecem informações para melhorar os protocolos de tratamento existentes, buscando uma farmacoterapia adaptada à idade e um uso mais seguro dos medicamentos em crianças e eventualmente em adultos.

Humans , Male , Female , Toxicology , Chagas Disease/diagnosis , Chagas Disease/drug therapy , Lactation/drug effects , Chagas Disease/etiology , Chagas Disease/ethnology , Pharmacologic Actions , Metabolic Side Effects of Drugs and Substances
Arq. bras. cardiol ; 112(3): 240-246, Mar. 2019. tab, graf
Article in English | LILACS | ID: biblio-989336


Abstract Background: In the past two decades, a new epidemiological profile of Chagas' disease (CD) has been registered in the Brazilian Amazon where oral transmission has been indicated as responsible for the increase of acute cases. In the Amazonas state, five outbreaks of acute CD have been registered since 2004. The cardiac manifestations in these cases may be characterized by diffuse myocarditis, with alteration in the electrocardiogram (ECG) and transthoracic echocardiogram (TTE). Objective: To perform a cardiac evaluation in autochthonous patients in the acute phase and at least one year after submitted to treatment for acute CD and evaluate the demographic variables associated with the presence of cardiac alterations. Methods: We evaluated patients diagnosed with acute CD through direct parasitological or serological (IgM) methods from 2007 to 2015. These patients were treated with benznidazole and underwent ECG and TTE before and after treatment. We assumed a confidence interval of 95% (CI 95%, p < 0.05) for all variables analyzed. Results: We observed 63 cases of an acute CD in which oral transmission corresponded to 75%. Cardiac alterations were found in 33% of the cases, with a greater frequency of ventricular repolarization alteration (13%), followed by pericardial effusion (10%) and right bundle branch block and left anterior fascicular block (2%). The follow-up occurred in 48 patients with ECG and 25 with TTE for a mean period of 15.5 ± 4.1 months after treatment. Of these, 8% presented normalization of the cardiac alterations in ECG, 62.5% remained with the normal exams. All of the patients presented normal results in TTE in the post-treatment period. As for the demographic variables, isolated cases presented more cardiac alterations than outbreaks (p = 0.044) as well as cases from Central Amazonas mesoregion (p = 0.020). Conclusions: Although cardiac alterations have not been frequent in most of the studied population, a continuous evaluation of the clinical-epidemiological dynamics of the disease in the region is necessary in order to establish preventive measures.

Resumo Fundamento: Nas últimas duas décadas, um novo perfil epidemiológico da Doença de Chagas (DC) foi registrado na Amazônia brasileira, onde a transmissão oral foi indicada como responsável pelo aumento dos casos agudos. No estado do Amazonas, foram registrados cinco surtos da doença desde 2004. As manifestações cardíacas nesses casos podem ser caracterizadas por miocardite difusa, com alteração nos resultados eletrocardiograma (ECG) e ecocardiografia transtorácica (ETT). Objetivo: avaliar parâmetros cardíacos em pacientes autóctones com DC na fase aguda e em um ano ou mais após tratamento, e avaliar as variáveis demográficas associadas com a presença de alterações cardíacas. Métodos: Avaliamos os pacientes diagnosticados com DC aguda por método direto parasitológico e exame sorológico (IgM) entre 2007 e 2015. Os pacientes foram tratados com benzonidazol e submetidos à ECG e ETT antes e após tratamento. Assumimos um intervalo de confiança de 95% (p < 0,05) para todas as variáveis analisadas. Resultados: Observamos 63 casos de DC aguda em que a transmissão oral ocorreu em 75% dos casos. Alterações cardíacas foram encontradas em 33% dos casos, com maior frequência de repolarização ventricular (13%), seguida de derrame pericárdico (10%), e bloqueio do ramo direito e bloqueio fascicular anterior esquerdo (2%). O acompanhamento foi realizado com 48 pacientes com ECG e 25 com ETT por um período médio de 15,5±4,1 meses após o tratamento. Desses pacientes, observou-se normalização das alterações eletrocardiográficas em 8% dos pacientes, e 62,5% continuaram com os parâmetros normais. Todos os pacientes apresentaram resultados da ETT normais no período pós-tratamento. Quanto às variáveis demográficas, os casos isolados apresentaram mais alterações cardíacas em comparação aos casos de surtos (p=0,044) e os casos identificados na mesorregião do Amazonas Central (p = 0,020). Conclusões: Apesar de as alterações cardíacas não terem sido frequentes na maioria da população do estudo, é necessária uma avaliação contínua da dinâmica clínica-epidemiológica da doença na região para se estabelecer medidas preventivas.

Humans , Male , Female , Adolescent , Adult , Young Adult , Trypanocidal Agents/therapeutic use , Chagas Cardiomyopathy/parasitology , Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Trypanosoma cruzi/isolation & purification , Brazil/epidemiology , Echocardiography , Chagas Cardiomyopathy/diagnostic imaging , Follow-Up Studies , Chagas Disease/complications , Chagas Disease/epidemiology , Electrocardiography
Rev. Soc. Bras. Med. Trop ; 51(6): 831-835, Nov.-Dec. 2018. graf
Article in English | LILACS | ID: biblio-1041490


Abstract INTRODUCTION: Chagas disease (CD) prevention and control rely on studies of its distribution, characteristics of individuals affected and mode of transmission. CD data in Brazil are scarce; a retrospective analysis of the clinical characteristics of 80 patients treated at the Clinical Hospital of UNICAMP, Campinas, Brazil, was performed. METHODS: Patient data records were analyzed. RESULTS: Thirty percent of the patients probably got infected through vector-borne transmission, 65% came from endemic areas, a predominance of cardiac and cardiodigestive forms was found among males, and the cardiac form prevailed (51%). CONCLUSIONS: The results update the view on the epidemiology of CD in Campinas, Brazil.

Humans , Male , Female , Hospital Records/statistics & numerical data , Chagas Disease/diagnosis , Chagas Disease/drug therapy , Chagas Disease/epidemiology , Brazil/epidemiology , Prevalence , Retrospective Studies , Middle Aged
Rev. Soc. Bras. Med. Trop ; 51(4): 557-559, July-Aug. 2018.
Article in English | LILACS | ID: biblio-957448


Abstract Chagas disease is a chronic parasitological disease, which could cause cardiac manifestations in approximately one-third of affected individuals. Benznidazole and nifurtimox are used to treat this parasitological infection caused by Trypanosoma cruzi. Conventionally, the criterion for cure is consistently negative serological tests after treatment. We report a case of a patient who was treated when she was 13 years old and achieved T. cruzi negative seroconversion but developed Chagas disease cardiomyopathy as an adult.

Humans , Female , Chagas Cardiomyopathy/diagnosis , Recurrence , Trypanocidal Agents/therapeutic use , Chagas Disease/drug therapy , Disease Progression , Middle Aged , Nitroimidazoles/therapeutic use
Rev. Soc. Bras. Med. Trop ; 51(3): 397-400, Apr.-June 2018. tab, graf
Article in English | LILACS | ID: biblio-957427


Abstract Atrial fibrillation (AF), a type of supraventricular arrhythmia increases the risk of thromboembolism. Chagas disease has been reported in the Brazilian Amazon region over approximately 20 years. Cardiac abnormalities are recorded in at least 50% of patients and among these, 3.3% develop AF. We describe a case of a 41-year-old man from Muaná, Pará State, who reported a 30-day history of a febrile illness. Acute Chagas disease was confirmed, and an electrocardiogram revealed AF. He was treated with antiparasitic and anti-arrhythmic drugs, beta blockers, and anticoagulants. Reversion to sinus rhythm was observed at his 9-month follow-up.

Humans , Male , Adult , Atrial Fibrillation/parasitology , Chagas Disease/complications , Atrial Fibrillation/diagnosis , Echocardiography , Acute Disease , Chagas Disease/diagnosis , Chagas Disease/drug therapy , Chagas Disease/transmission , Electrocardiography
Ciênc. Saúde Colet ; 23(5): 1483-1494, Mai. 2018. tab
Article in Portuguese | LILACS | ID: biblio-890596


Resumo O Serviço de Atenção Farmacêutica ao paciente com doença de Chagas do estado do Ceará foi criando em 2005, com a finalidade de proporcionar seguimento farmacoterapêutico àqueles com esta morbidade. Decorridos 10 anos de atuação, objetivou-se avaliar a satisfação dos pacientes atendidos no serviço. Tratou-se de um estudo prospectivo, empregando um questionário subdividido nas seções: dados socioeconômicos; infraestrutura, localização e funcionamento; cuidado farmacêutico e importância do serviço. Foram entrevistados 70 pacientes de ambos os sexos e acima de 18 anos, entre agosto de 2014 e maio de 2015. Quanto à infraestrutura, localização e funcionamento, as notas obtidas mostraram que os pacientes estão satisfeitos com os parâmetros analisados. Com relação ao cuidado farmacêutico, a maioria dos pacientes mostrou-se satisfeita, tendo o "ser bem atendido" como aspecto mais importante durante o atendimento. Em relação à importância do serviço, 100% o considerou muito importante e o indicaria para outras pessoas. De modo geral, o estudo demonstrou um alto nível de satisfação com o serviço. Há muito a ser trabalhado neste serviço, como promover maior acesso e qualificação do atendimento, contribuindo para a concretização de um modelo humanizado, centrado nas necessidades do paciente.

Abstract In 2005, a pharmaceutical care service was created in the State of Ceará to provide pharmacotherapeutic follow-up for individuals infected with Trypanosoma cruzi (Chagas Disease). After 10 years of operation, an evaluation was conducted to assess the degree of satisfaction of patients treated under the service. This prospective study used a questionnaire comprising the following sections: socioeconomic data; infrastructure, facilities and operations; pharmaceutical care; and importance of the service. Seventy patients of both sexes and over 18 years of age were interviewed between August 2014 and May 2015. As for infrastructure, location and operation, the average grades show a high level of patient satisfaction. Regarding pharmaceutical care, most patients reported being satisfied and considered "being well treated" to be the most important aspect during treatment. In addition, all patients (100%) rated the service as very important and would recommend it to other individuals. Overall, the study showed a high level of patient satisfaction with the service. There is, however, still much to work to be done on this service in order to promote greater access and qualified care to fully achieve a humanized model focused on patient needs.

Humans , Male , Female , Adolescent , Adult , Young Adult , Pharmaceutical Services/organization & administration , Patient Satisfaction/statistics & numerical data , Chagas Disease/drug therapy , Socioeconomic Factors , Brazil , Prospective Studies , Surveys and Questionnaires , Middle Aged
Rev. Soc. Bras. Med. Trop ; 51(2): 133-140, Mar.-Apr. 2018. tab
Article in English | LILACS | ID: biblio-897057


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.

Animals , Trypanocidal Agents/administration & dosage , Chagas Disease/drug therapy , Dose-Response Relationship, Drug , Nitroimidazoles/administration & dosage , Chronic Disease , Disease Models, Animal , Mice
An. acad. bras. ciênc ; 90(1,supl.1): 645-661, 2018. graf
Article in English | LILACS | ID: biblio-886933


ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry's striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC) of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

Humans , Trypanocidal Agents/chemistry , Chemistry, Pharmaceutical , Drug Discovery/methods , Neglected Diseases/drug therapy , Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Schistosomiasis/drug therapy , Tropical Medicine/trends , Chagas Disease/drug therapy
Acta bioquím. clín. latinoam ; 51(4): 687-694, dic. 2017. graf, map, tab
Article in Spanish | LILACS | ID: biblio-886152


El objetivo del trabajo consistió en identificar la seroprevalencia de la infección por Trypanosoma cruzi en niños en edad escolar en localidades de las provincias de Salta y Chaco. Se trabajó en 44 escuelas de la ciudad de Salta, en parajes de San Carlos; en 10 escuelas de La Unión y en 7 escuelas de Taco Pozo. El trabajo tiene un diseño de corte transversal. La toma de muestra se realizó por punción capilar con equipos Serokit, y la confirmación de los casos seropositivos o dudosos por punción venosa, y obtención de suero, para realizar HAI y ELISA. Los casos seropositivos confirmados fueron tratados con Benznidazol® durante 60 días en dosis de 5-7mg/kg/ día. Para el análisis estadístico se elaboraron tablas con frecuencias absolutas y relativas. Se analizaron 17.884 escolares y se detectaron159 seropositivos, siendo la mayor seroprevalencia en la localidad de La Unión y la menor en la ciudad de Salta. Se aplicó tratamiento a 93 niños (71,54 %) de la ciudad y en el ámbito rural se trataron todos los casos. La vía de infección vectorial fue la de mayor predominio en las madres (64,47%). Se concluye que aunque la seroprevalencia fue menor en la ciudad de Salta que en las zonas rurales, es necesario continuar con la vigilancia.

The aim of this work was to identify seroprevalence of Trypanosoma cruzi infection in school-age children who live in localities from Salta and Chaco. This work was conducted in the following schools: 44 located in Salta city, 10 in La Unión, 7 in Taco Pozo, and several in rural spots around San Carlos town. The design was cross-sectional and the samples were taken by capillary punction with Serokit equipment. Seropositive cases were confirmed by HAI and ELISA performed on serum obtained by venous punction. Confirmed seropositive cases were treated with Benznidazol® for 60 days in doses of 5-7 mg/kg/day. Tables with absolute and relative frequencies were made for statistical analysis. It resulted that the number of school-aged children analyzed was 17,884, 159 being seropositive. The highest seroprevalence was detected in La Unión and the lowest in Salta city. Treatment was given to 93 children (71.54%) from Salta city, while every child was treated in rural areas. Infections in mothers was vector-borne mainly (64.47%). It can be concluded that even though seroprevalence was lower in the city of Salta than in rural areas, it is important to continue monitoring for Chagas disease.

O objetivo do trabalho consistiu em identificar a soroprevalência da infecção por Trypanosoma cruzi em crianças em idade escolar em localidades das províncias de Salta e de Chaco. O trabalho foi realizado em 44 escolas da cidade de Salta, em paragens de San Carlos; em 10 escolas de La Unión e em 7 escolas de Taco Pozo. O mesmo tem um desenho de corte transversal. Tomada de amostra: foi realizada por punção capilar com equipamentos Serokit e a confirmação dos casos soropositivos ou duvidoso por punção venosa e obtenção de soro, para realizar HAI e ELISA. Os casos soropositivos confirmados foram tratados com Benznidazole® durante 60 dias em doses de 5-7 mg/kg/dia. Para a análise estatística foram preparadas tabelas com frequências absolutas e relativas. Analisaram-se 17.884 crianças detectando 159 soropositivos, sendo a maior soroprevalência na cidade de La Unión e a menor na cidade de Salta. Aplicou-se o tratamento a 93 crianças, (71,54%) da cidade e na área rural se trataram todos os casos. A via de infecção vetorial foi a de maior predominância nas mães (64,47%). Conclui-se que embora a soroprevalência tenha sido menor na cidade de Salta do que nas áreas rurais, é necessário continuar com a vigilância.

Humans , Male , Female , Child , Adolescent , Chagas Disease/diagnosis , Chagas Disease/drug therapy , Chagas Disease/ethnology , Prevalence , Chagas Disease/classification , Parasitology
Infectio ; 21(4): 255-266, Oct.-Dec. 2017. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-892740


Abstract Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. To generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: «Chagas disease/congenital¼, «prevention and control¼, «diagnosis¼, «therapeutics¼ and «pregnancy¼. Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-to-face discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia.

Resumen La transmisión congénita de la enfermedad de Chagas ha sido poco estudiada en Colombia y existen pocos procedimientos rutinarios en el sistema de salud para el manejo de esta enfermedad. Por ello se desarrolló un consenso de expertos dirigido a generar recomendaciones de diagnóstico y tratamiento de Chagas con- génito y orientación a mujeres en edad fértil. Con ese propósito se realizó una búsqueda extensiva de la literatura, empleando una combinación de términos Mes (Chagas, Chagas congénito, prevención, control, diagnóstico, tratamiento y embarazo) para reflejar el estado del arte en cada tema de interés. Después de ello, se leyeron los resúmenes y aquellos seleccionados para análisis del texto completo. La literatura relevante se sintetizo, clasifico y organizo en tablas y se presentó al panel de expertos, el cual estaba constituido por 30 profesionales en diferentes áreas. Mediante la metodología Delphi se realizaron 2 rondas de cuestionarios virtuales y una reunión presencial en los cuales se evaluaron los niveles de acuerdo entre los participantes. Los puntos con falta de consenso durante las 2 rondas virtuales se expusieron durante las mesas de discusión en la ronda presencial. La evidencia utilizada se adaptó a las particularidades nacionales según el caso y se aprobó el contenido del documento final. Se propone que estas recomendaciones sean usadas por profesionales de la salud en Colombia.

Humans , Female , Adolescent , Adult , Chagas Disease/congenital , Consensus , Orientation/physiology , Chagas Disease/drug therapy , Colombia
Rev. Soc. Bras. Med. Trop ; 50(6): 748-755, Nov.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-897032


Abstract The pharmacological management of adults with chronic-phase Chagas disease is challenging despite it being the recent focus of extensive research. One of the challenges in the current clinical practice guidelines (CPGs) landscape is the existence of non-evidence-based recommendations for the use of laboratory tests in treatment monitoring. This study aimed to systematically assess the quality and consistency of recommendations of CPGs on the pharmacological management of adults with chronic-phase Chagas disease. Systematic literature searches were conducted in MEDLINE, EMBASE, SciELO and Google to identify all published CPGs relevant to the pharmacological management of Chagas disease, between January 2010 and March 2016. Three independent reviewers assessed the quality of each CPG using the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. A total of five CPGs were included and the overall quality of the guidelines for therapeutic drug monitoring of Chagas disease was moderate-to-low. There was considerable variation in the quality of the CPGs across the AGREE II domains. The domains of scope/purpose, stakeholder involvement, and clarity of presentation were rated well, and the domains of applicability and editorial independence received poor ratings. This review showed that the methodological quality of CPGs for Chagas disease was generally inappropriate, and there was no explicit link between the best available evidence and current recommendations.

Humans , Trypanocidal Agents/therapeutic use , Drug Monitoring , Chagas Disease/drug therapy , Practice Guidelines as Topic , Nifurtimox/therapeutic use , Nitroimidazoles/therapeutic use , Chronic Disease
Rev. Soc. Bras. Med. Trop ; 50(3): 334-340, May-June 2017. tab
Article in English | LILACS | ID: biblio-896976


Abstract INTRODUCTION Benznidazole (BNZ) is a drug available for the etiological treatment of Chagas disease. However, this drug is toxic and has a limited effectiveness on the chronic phase of this disease, often leading to poor treatment adherence. METHODS: This is a descriptive and exploratory study conducted at the Pharmaceutical Care Service for Chagas disease patients of the Federal University of Ceará. Drug-related problems (DRPs) and pharmaceutical interventions (PIs) were classified according to the Second Consensus of Granada. RESULTS: The average age of patients with Chagas disease was 62 years, with the majority residing in the Ceará countryside (86.7%), and having low education levels (63.3% with elementary school education). Regarding family income, most patients belonged to a household that earned ≤1-2 times the minimum wage per month. Approximately 73% of these patients complied with the BNZ treatment, and nearly 7% underwent therapy interruption after medical evaluation. A total of 189 DRPs were identified, of which 51.9% (n=98) were classified as potential, and 48.1% (n=91) as actual. The most frequent DRPs were related to safety (qualitative safety; n=70; 37%), necessity (non-adherence; n=52; 27.5%), and effectiveness (qualitative effectiveness/non-optimal drug selection; n=45; 23.8%). Among the 216 PIs conducted, the majority were related to patient education (n=168; 77.8%) and pharmacological strategy (n=42; 19.4%). CONCLUSIONS: This study indicates the need for pharmacotherapeutic monitoring in patients with Chagas because of the high number of therapeutic interventions, DRPs (approximately 3 DRPs/patient), BNZ adherence, and polypharmacy.

Humans , Male , Female , Trypanocidal Agents/therapeutic use , Chagas Disease/drug therapy , Drug-Related Side Effects and Adverse Reactions/classification , Medication Adherence/statistics & numerical data , Nitroimidazoles/therapeutic use , Socioeconomic Factors , Trypanocidal Agents/adverse effects , Brazil , Follow-Up Studies , Middle Aged , Nitroimidazoles/adverse effects
Rev. Soc. Bras. Med. Trop ; 50(3): 296-300, May-June 2017. tab
Article in English | LILACS | ID: biblio-896973


Abstract After more than one century since its discovery, Chagas disease is still extremely prevalent in 21 Latin American countries. Chagas disease is one of the most concerning public health problems in Latin America; the overall cost of CD treatment is approximately 7 billion United States dollars per year and it has a strong social impact on populations. Little progress has been made regarding the access to diagnosis and treatment at the primary health care level, calling into question the current policies to ensure the right to health and access to essential medications. In this article, diverse dimensions of access to treatment for Chagas disease are reviewed, illustrating the present state of benznidazole medication in relation to global production capacity, costs, and needs. The findings are based on an investigation requested by Médecins Sans Frontières Brazil through a consultancy in 2015, aiming to estimate the current costs of benznidazole production.

Humans , Trypanocidal Agents/therapeutic use , Drug Costs/statistics & numerical data , Chagas Disease/drug therapy , Health Services Accessibility , Nitroimidazoles/therapeutic use , Trypanocidal Agents/economics , Brazil , Chagas Disease/economics , Health Services Needs and Demand , Latin America , Nitroimidazoles/economics