Avaliação terapêutica duplo-cega baseada na técnica do oograma quantitativo, comparando praziquantel com oxamniquine na esquistossomose mansônica humana

Um total de 54 pacientes adultos, com esquistossomose mansônica crônica, nas formas intestinal ou hepatintestinal, participou de um ensaio clínico duplo-cego, para comparar o praziquantel com a oxamniquine. De acordo com uma distribuição aleatória, 27 casos receberam o praziquantel (65 mg/kg de peso corporal) e 27 a oxamniquine (18 mg/kg), administrados em dose oral única. A incidência, intensidade e duração dos efeitos colaterais foram similares para os dois medicamentos A avaliação da eficácia terapêutica baseou se na técnica do oograma quantitativo por biópsia da mucosa retal, realizada ao final de um, dois, quatro e seis meses depois do tratamento. Nessas mesmas ocasiões foram feitos exames de fezes pelos métodos de HOFFMAN, PONS e JANER e de KATO-KATZ, com a finalidade de confrontar seu resultados com os achados do oograma. Para averiguar o efeito imediato do tratamento sobre a atividade ovipositora do parasito, um número restrito de pacientes foi submetido a biópsias retáis no 6,° e 18.° dias subsequentes a administração da medicação. Ambas as drogas provaram ser ativas contra o esquistossoma, vez que os respectivos coeficientes de variação, determinados a partir de oogramas efetuados imediatamente após o tratamento, foram superiores a 60%. Ademais, dentre os 27 pacientes de cada grupo, 24 tratados com praziquantel e 22 com oxamniquine completaram o período de seis meses, requerido para controle parasitológico. Os índices de cura, segundo os achados do oograma e dos exames de fezes pelos métodos de HPJ e KK, foram, respectivamente, 29%, 50% e 92% com o praziquantel; 23%, 50% e 86% com a oxamniquine. Apesar do baixo percentual de cura, observou-se nos oogramas pós tratamento, uma pronunciada queda no número de ovos vivos por grama de tecido. Esses resultados revelam que ambas as drogas foram semelhantemente eficazes, embora já se tenha comprovado que a susceptibilidade do S. mansoni não seja sempre igual para cada um desses medicamentos, pois linhagens resistentes à oxamniquine evidenciaram ser 100% sensíveis ao praziquantel. Por outro lado, constatou-se uma nítida diferença nos percentuais de cura em função do método utilizado para controle parasitológico. O oograma foi o mais preciso, seguido pelo HPJ e, finalmente, pelo K-K. Tendo ocorrido uma correlação direta entre o número de ovos vivos no oograma e a positividade dos exames de fezes, a percentagem de resultados falso-negativos aumentou acentuadamente após o tratamento, alcançando 47,3% com o HPJ e 92,9% com o K-K. Antes da medicação esses índices eram, respectivamente, 0% e 64,8%. Os autores depreendem que a diferença de precisão da metodologia aplicada para avaliar a eficácia terapêutica pode explicar a divergência encontrada entre o índice de cura obtido neste - ensaio clínico e os relatados por outros investigadores, tanto com o praziquantel quanto com a oxamniquine.A total of 54 adult patients with chronic intestinal or hepato-intestinal schistosomiasis mansoni were included into a double-blind clinical trial to compare praziquantel and oxamniquine. Following a randomized allocation, 27 patients received praziquantel 65 mg/kg bwt and 27 oxamniquine 18 mg/kg bwt in a single oral dose divided into two intakes. The incidence, severity and duration of side-effects were similar for the two drugs. The assessment of therapeutical efficacy was based on the quantitative oogram technique via biopsy of the rectal mucosa, performed at the end of 1, 2, 4 and 6 months after treatment. At these same occasions, stool examinations according to Hoffman, Pons & Janer (HPJ) and Kato-Katz (K-K) methods were undertaken to confront their results with the oogram findings. In order to evaluate the immediate effect of the therapy upon the egg laying activity of the parasite, a limited number of patients was submitted to rectal biopsies on the 6th. and 18th. days subsequent to the drug administration. Both drugs proved to be active anti-schistosomal agents as their coefficients of variation, determined from the oograms made immediatly following the treatment, were above 60%. Furthermore, out of 27 patients in each group, 24 treated with praziquantel and 22 with oxamniquine have completed the required six months parasitological follow up period. The respective cure rates in accordance with the oogram, HPJ and K-K findings were: 29.2%, 50% and 91.7% for praziquantel; 22.7%, 50% and 86.3% for oxamniquine. Despite a quite low cure rate, a sharp fall (-83%) in the mean number of living eggs per gram of tissue was observed in the post-treatment oograms. These results indicated that both anti-schistosomal agents were similarly efficacious On the other hand, a striking difference in the cure rates amongst the three parasitological control methods became evident. The oogram was the most accurate one, followed by HPJ and lastly by K-K. Since there was a direct correlation between the number of living eggs in the oogram and the positivity of the stool examinations, the percentage of false-negative results has augmented remarkably after treatment reaching 47.3% with HPJ and 92.9% with K-K. Prior to therapy they were 0% and 64,8%, respectively. The authors infer that the different accuracy of the applied methodology to assess therapeutical efficacy may explain the discrepancy between the cure rate achieved in this clinical trial and those reported by other investigations with either praziquantel or oxamniquine

Analysis of Three-Dimensional Scar Architecture and Conducting Channels by High-Resolution Contrast-Enhanced Cardiac Magnetic Resonance Imaging in Chagas Heart Disease

We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events.Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range).A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60).High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events

Disfagia orofaríngea na doença de Chagas crônica: avaliação fonoaudiológica, videofluoroscópica e esofagomanométrica

Objetivo: Em pacientes chagásicos crônicos, determinar a frequência dos episódios de penetração e aspiração laríngea e avaliar sua relação de interpretação, não só com os padrões exibidos na videofluoroscopia e na esofagomanometria, mas também, com a triagem clínica, a avaliação fonoaudiológica estrutural e funcional. Método: 22 indivíduos foram incluídos no estudo, sendo 15 mulheres e 7 homens, média de idade de 55,9 ± 10,2. Os pacientes foram submetidos à avaliação clínica, fonoaudiológica (estrutural e funcional), e aos exames de videofluoroscopia e esofagomanometria computadorizada. Resultados: Dentre as queixas na triagem clínica, 18,2% relataram engasgos, 13,6% pigarro, 40,9% azia, 22,7% regurgitação e 36,4% sensação de alimento parado na garganta. Apenas 18,2% apresentavam uma dentição adequada. Na avaliação funcional da deglutição 31,8% tiveram diagnóstico de deglutição funcional. Na videofluoroscopia foi encontrada permanência de resíduos na faringe em 18,2% dos casos, seguida de deglutições múltiplas em 95,4% e escape posterior em 100%. Observou-se 4 casos de penetração laríngea de grau 2 (disfagia) e em 82% dos casos os achados foram semelhantes entre a videofluoroscopia e avaliação funcional da deglutição, quanto a não ocorrência de penetração laríngea. Os valores de abertura do esfíncter esofágico superior indicam uma relação com o volume de bolo deglutido. Já na manometria foram encontrados 42,1% de alterações em corpo do esôfago e 5,3% em faringe. Conclusão: A penetração laríngea foi prevalente em 18,2% dos casos com uma relação de interpretação importante entre a avaliação fonoaudiológica funcional e os achados videofluoroscópicos, quanto à ausência de penetração laríngea, com resultados semelhantes em 82% dos casos.Objective: To determine the frequency of episodes of laryngeal penetration and aspiration in chronic Chagas patients and to evaluate the interpreted relationship not only with the patterns displayed in videofluoroscopy and manometry, but also with clinical screening and structural and functional phonoaudiological evaluation. Method: Clinical and phonoaudiological (structural and functional) evaluation, fluoroscopy, and computed manometry were performed on all patients. Results: Twenty-two patients were included in the study, fifteen females and seven males. Age ranged between 37 and 70 years, mean 55.9 ± 10.2 years. Among the complaints in clinical screening, 18.2% were choking, 13.6% reported throat-clearing, 40.9% heartburn, 22.7% regurgitation, and 36.4% had the sensation of food stuck in the throat. Only 18.2% of patients had adequate dentition. Functional assessment of swallowing detected only 31.8% capable of functional swallowing. In videofluoroscopy, lingering residues were found in the pharynx in 18.2% of cases, followed by multiple swallows 95.4% and 100% posterior escape. There were 4 cases of grade 2 laryngeal penetration (dysphagia) and, in 82% of cases, the findings were similar for the non-occurrence of laryngeal penetration in the videofluoroscopy and in the functional assessment of swallowing. The apertures of the upper esophageal sphincter indicated a relationship with the volume of swallowed bolus. In the manometry, 42.1% of changes were found in the body of the esophagus and 5.3% in the pharynx. Conclusion: Laryngeal penetration was prevalent in 18.2% of cases with an important interpretation of the functional relationship between clinical assessment and videofluoroscopic findings regarding the absence of laryngeal penetration, with similar results in 82% of cases