Gallerano R R, Sosa R R
Cátedra de Medicina I, Universidad Nacional de Córdoba, Servicio de Clínica Médica Hospital Córdoba.
Rev Fac Cien Med Univ Nac Cordoba. 2000;57(2):135-62.
In this study is presented the comparative therapeutical experience comparing the Allopurinol, Benznidazol y Nifurtimox, in a prospective following in a long term, considering the responses to the parasitemia, specific serology and evolution of the clinic manifestations and complementaries in the 535 chronic chagasic cases (44.5%), instead of 668 patients who did not get any treatment (1203 chagasic cases followed for more than 5 years average). This study was done between April 1984 and April 1994 in patients with and without cardiopathy, in the Córdoba Hospital and the Salud Estudiantil Direccion, Universidad Nacional de Córdoba (U.N.C.); from them, 309 patients were given Allopurinol, 130 were given Benznidazol, and 96 were given Nifurtimox, with usual doses of Benznidazol and Nifurtimox, but with Allopurinol it was made an study evaluating the answering-doses, with a following time of post-therapeutic average of 55.6 months (D.S. = + -57 m.) The comparative parameters were the starting clinic characteristics, the qualitative and quantitative for Chagas, the pre-treatment xerodiagnostic, the treatment fulfillment, the treatment duration, the adverse effects, the treatment abandon, the time of postreatment longitudinal following till the last clinic-complementary evaluation, the clinic characteristics at the end of the following period; quantitative and qualitative serology for Chagas after the treatment, and post-treatment xerodiagnostic. It was observe a prevalence of Electrocardiographic Changes in the ECG in rest, in the first complementary evaluation in 76 of the 535 "Treated" and in the 225 "No-treated" patients, being Electrocardiographic abnormality proportion much more in the "No-treated" patients (P = 0.000000). After the end of the following period it was thought to have been found Miocardic Damage Progression in 120 patients "No-treated" and in 31 "Treated" patients (17.9% and 5.8% respectively) (P = 0.0000000). The complications in the evolution course were proved in 113 of the "No-treated" and in 19 of the "Treated" patients (16.9% and 3.5%, being this a statistically significant difference (P = 0.0000000). The mortality along the evolution was proved in 37 of the "No-Treated:" patients and in 7 of the "Treated" patients (5.5% and 1.3%), being this a statistically significant difference (P = 0.00019). The most tolerated drug and the one with the least incidence of therapeutic abandons was the Allopurinol. The xerodiagnostic negativization percentages were 72.5% for Allopurinol, 76.4% for Benznidazol and 76.5% for Nifurtimox (non-significant differences). A year and two years after the end of the treatment was made a titled serology with the Inmunofluorescence and Indirect Hemoaglutination Tests, getting significant statistical differences between the three drugs, resulting lower the values obtain after the treatment with Benznidazol and Nifurtimox than with Allopurinol (P = 0.0042 and P = 0.00039), respectively). The biggest proportion of Progression in the Cardiopathies, Complications, General Mortality and Attributed Mortality in "No Treated" (specially in older than 30 years) significant both for infected patient and slight cardiopathy, stabilises the possibility of stopping or reducing the morbid course of the Chronic Chagasic Cardiopathy, specially relevant in the formers, where the pathogenic process seems to be accelerated related to the latters. The negativation of the parasitemia and the parasitemia and the title disminution of the specific serology like effectiveness treatment parameters, and the stopping in the progression or dissemination of the incidence in new cases of Chronic Chagasic Cardiopathies were considered to be the real benefit of the antiparasitaric therapeutic in the Chagas Disease. As a conclusion, it is thought that the further the instauration of the specific antiparasitaric treatment the more the possibilities of effectiveness, as well as the increase in the probabilities of preventing or reducing the incidence of cardiopathy in chronic infected, or to stop its evolution and reduce its morbimortality in patients with already installed cardiopathy.
本研究展示了对别嘌醇、苯硝唑和硝呋替莫的比较治疗经验,这是一项长期前瞻性研究,观察了535例慢性恰加斯病患者(占44.5%)对寄生虫血症、特异性血清学检查的反应以及临床表现和辅助检查结果的演变,而非668例未接受任何治疗的患者(共1203例恰加斯病患者,平均随访超过5年)。本研究于1984年4月至1994年4月在科尔多瓦医院和科尔多瓦国立大学(U.N.C.)学生健康管理部门对有或无心脏病的患者进行;其中,309例患者服用别嘌醇,130例患者服用苯硝唑,96例患者服用硝呋替莫,苯硝唑和硝呋替莫采用常规剂量,但对别嘌醇进行了剂量反应研究,治疗后平均随访时间为55.6个月(标准差=±57个月)。比较参数包括初始临床特征、恰加斯病的定性和定量指标、治疗前的干血片诊断、治疗依从性、治疗持续时间、不良反应、治疗中断情况、治疗后至最后一次临床辅助检查的纵向随访时间、随访期结束时的临床特征;治疗后恰加斯病的定量和定性血清学检查以及治疗后的干血片诊断。在535例“治疗组”和225例“未治疗组”患者的首次辅助检查中,静息心电图显示心电图改变的发生率较高,“未治疗组患者的心电图异常比例更高(P = 0.000000)。随访期结束后,120例“未治疗”患者和31例“治疗”患者被认为出现了心肌损伤进展(分别为17.9%和5.8%)(P = 0.0000000)。“未治疗组”113例患者和“治疗组”19例患者在病程中出现了并发症(分别为16.9%和3.5%,这是一个具有统计学意义的差异(P = 0.0000000)。“未治疗组”37例患者和“治疗组”7例患者在病程中出现了死亡(分别为5.5%和1.3%),这是一个具有统计学意义的差异(P = 0.00019)。耐受性最好且治疗中断发生率最低的药物是别嘌醇。别嘌醇、苯硝唑和硝呋替莫的干血片诊断转阴率分别为72.5%、76.4%和76.5%(无显著差异)。治疗结束一年和两年后,采用免疫荧光和间接血凝试验进行特异性血清学检查,三种药物之间存在显著的统计学差异,苯硝唑和硝呋替莫治疗后获得的值低于别嘌醇(分别为P = 0.0042和P = 0.00039)。“未治疗组”(尤其是30岁以上患者)在心脏病进展、并发症、总体死亡率和归因死亡率方面的比例最高,这对于感染患者和轻度心脏病患者都具有重要意义,稳定了阻止或减轻慢性恰加斯病心脏病病程的可能性,这在前者中尤为重要,因为其致病过程似乎比后者加速。寄生虫血症转阴、特异性血清学滴度降低作为治疗效果参数,以及慢性恰加斯病心脏病新发病例发病率的进展或传播停止被认为是恰加斯病抗寄生虫治疗的真正益处。总之,认为尽早开始特异性抗寄生虫治疗,有效性的可能性就越大,同时预防或降低慢性感染者心脏病发病率的概率增加,或者在已患心脏病的患者中阻止其进展并降低其病死亡率的概率也增加。