Chronical Chagas Illnes: Controversial
aspects about its ethiological treatment.
Rafael E. Manzur, Gustavo Barbieri
Center of Chagas Illness and Regional Pathology
"Dr. Humberto Lugones"
Santiago del Estero, Argentina
The treatment of Chagas illness in its chronic phase has arised many controversies about its application. In the 80's many investigators began to use those compounds in this phase of the illness, with the justification of controlling an evolutive known process; to be able to erradicate the parasite from the blood and eliminate with this, the human reserves of the parasite designed to interrupt the chain of transmission; diminish the incidence both post transfusional and congenital Chagas and thus preventing the appearance of cardiopaties.
The published studies about the clinical evolution of the illness after the treatment, offer controversial results due to the methods used for the evaluation, the scarce of cases and also for the control of the studies.
Among the serological methods we use the indirect hemaglutination (HAI), indirect inmunofluorescence (TIF) and the Elisa. The diagnosis rules since 1995 already stated the treatment in latent phase till 5 years and according to medical criteria, the convenience of extending till older children.
Those rules were modified in 1998 and stated the treatment in latent phase and adults. We think that scientific reliable information must be produced, though multicentric studies, to put light on dark points and we should revise criteria to evaluate cure; this is a particularly complex situation that creates difficulties in relation to clinical, serological and parasitological aspects. At the same time, we think it is advisable to go on searching new drugs for the treatment of the illness with the requirements of WHO.
The population of Argentina is about 33 million of in habitants  and shows variables in the prevalence of patients with positive serology, going from 2% to 11% [2-3] according to the (endemicity) of the region.
In high (endemic) region, 6,3 million people [4-5] are exposed to develop a miocardic illness both in its delayed phase and in the phase related to problems of conduction, according to the evolutive way, and influenced by regional factors, inmunological state, socio economic conditions and parasite stub.
The infection is characterized for a sharp oligosymptomatic phase, a latent phase or without determined symptoms and a symptomatic chronical phase . If we observe the group of asymptomatic seropositive patients during the evolution that can last decades, about 25 to 30% present symptoms and signs in the level of the central nervous system, digestive system and particularly in the cardiovascular system, a group of patients have a cardiac compromise without clinic manifestations and a 10% present clinic manifestations, due to specific alterations of muscular fibers in the conduction systems, whose symptoms of cardiac insufficiency are associated to a disorder in that particular system.
With the object of controlling Chagas and since 1960 with
the creation of the National Chagas program, the following measures were proposed:
a) elimination of the vector insect.
b) chimiotherapy of infected patients with efficient drugs to eliminate human reserves of Tripanosoma Cruzi .
c) control of blood banks.
d) control of congenital transmission.
Antecedents of therapy with ethiological
Salvador Mazza began to use the ethiological treatment in 1937 for Chagas illness using Bayer 7602, Bayer 9736 and M 3024 compounds or Cruzon . Since 1965 Nifurtimox  was used, with good results in patients coursing the sharp phase of the infection.
Since 1969 many clinical and lab studies showed the effectiveness of tripanomicida of Nifurtimox and Benznidazol drugs during the sharp phase with therapeutic effectiveness till an 80% [10-19]; anyway, they were not considered ideal drugs [10,20-22] due to the appearance of varied secondary effects [23-25] whose most evident manifestations were observed in grown up patients [26-30].
From the 80's many investigators began to use those compounds
in chronical phases of the illness; the reason for its application were:
a) to leave the position of mere spectators in a known evolutive process.
b) to eradicate the parasite from the blood (fundamental for the actions of controlling and eliminating the human reserves of the parasite to interrupt the chain of transmission of the illness).
c) to diminish the incidence both of the post transfusional and congenital Chagas.
d) to prevent the appearance of cardiopathies [31,32].
The demonstration of the presence of the T. Cruzi or its fractions, whose direct action would damage the miocardic level producing chronic miocardiopathy with signs of active inflamatory process, demonstrated by different inmunohistochemical and molecular techniques (PCR)  has oriented investigators about the need to eliminate the parasite from textures to prevent future lesions .
Although the presence of fractions of T. Cruzi in the inner miocardic is given the responsibility of tisular damage through mechanisms of direct action , it is also proposed that the productions of alterations  by the effect of inflammatory citokinas and reactions or maintained by T cells, with crusade reactivity antimiocardic.
Besides, it is possible the participation of anticorps against the thermic protein of stress HSP .
Based on the mechanisms of miocardic aggression, in 1983 the National Ministry of Health gave the rules for the application of treatment , recommending its application only for cases of sharp Chagas, using the two drugs that were available al that moment (Benznidazol and Nifurmitox), including those lactants who are more than 6 months with persistence of positive serologic congenital Chagas. These rules established that the parasitologic, serologic and clinic studies made in chronic patients did not demonstrate the profit of ethiological treatment; for this reason those should not be treated; in the other hand, the frequency of serious colateral effects  in some patients receiving this treatment.
During the chronical phase the infected patient treated with the specific tripanomicida drug showed a similar evolution to that of seropositive patients for Chagas illness; that's why, it lacked bases for its application, using as criteria of cure, serologic negativeness which caused different opinions of different authors [38-39].
Romeo Cançado is the one who, in certain way, began the controversy in 1969 when he described the persistence of positive serology in chronical patients treated with tripanomicida, made in controlled studies, applied to that object, parasitological, xeno and serological cure criteria; in this way we see that controversy has been present for a long time [32-40].
Different developed and published studies about the clinic evolution of the illness after treatment with the drugs in use, offer controversial, not very convincing results, particularly due to the methods used for their evaluation, because of few cases shown and also because of the used controls.
In works done by Brazilian and Argentine investigators in chronic patients [24-31], clinic evolution measured in periods of 7 to 8 years did not offer significant differences, related to not treated patients. The appearance of alteration in ECG were very low, thus interpretation of obtained data was difficult, because the comparison between them does not offer significant results.
Before and after the specific treatment of Chagas we recommend rutinary parasitological exams because the reduction of parasitemia or its negativeness suppose to minimize the risk of the evolution to a cardiopathy or rather stop it when it is in course. Some investigators require total disappearance of anticorps as requisite to assure the cure [41-42]. The existence of parasites after the tripanomicida treatment would indicate a failure in this aspect.
Among the serological methods used as cure criteria, the indirect hemaglutination (HAI), the indirect inmunofluorescence (TIF) and the inmunoenzimatic procedure of ELISA , techniques that should be used, because they allow to compare the concentration of anticorps before, during and after the treatment and to be aware of the existence of individual differences in each serological reaction, in relation to the title of the individual samples of serum. Each infected individual reacts in a different way to the existent antigens in the parasite, both in relation to the affinity of each anticorp and in front of a different number of anticorps .
The diagnosis rules, given in 1995  already stated the treatment for children in latent phase and until 5 years, and left to medical criteria the convenience to go until older children. It has to be assumed that the treatment has been barely efficient if in a period from 5 to 10 years of control, there are observed results of negative parasitology with persistence of positive serologic reactions, using tests with conventional serology.
It would be advisable that the design of studies designated
to evaluate the therapeutic efficiency includes the practice of serologic reactions
with different techniques and with conventional and recombinated antigens, thus
allowing the comparison of concentration of initial anticorps with the results
during the periodical controls. The determination of high levels of serological
titles, states questions that can be related with answers such as:
a) more agresiveness to damage miocardio.
b) persistent presence of parasitemia.
c) more number of parasites.
d) presence of reinfection (in patients in no controlled endemic areas).
Precocius diagnosis and the beginning of specific treatment, in houses under entomologic control can be good signs for better possibilities of obtaining parasitological cure .
Sosa Estain's and de Andrade's works [31-47] with similar controlled designs, applied a cure criteria based on the negativeness and/or reduction of serology titles and negativeness of Xenodiagnosis. In Sosa Estain's work  there was introduced the use of a recombinating Ag as a marker of serologic cure, gaining in this way a therapeutic efficiency with the BZ from 55 to 62%.
Afterwards, rules from 1983 were modified  and in our country new rules were elaborated in June, 1998 .
Those rules advise the treatment for:
a) Every patient in the sharp phase of the illness.
b) Children and teen agers in latent phase.
c) Adults in latent phase or incipient or asymptomatic cardiac pathology of the illness.
d) Accidents with contaminated material or with surgeries.
e) Givers or receptors in transplantation of organs.
Hose resolutions were not completely accepted by the investigators, that's why some people accept them with some precautions and only apply the treatment until 12 years old . We understand that the secondary manifestations that the administration of BZ produce, are more important with age, so medication in adults implies a bigger risk, with appearance of phenomena of periferic neuritis, digestive and dermatologic problems (Steven -Johnson), etc.
In those cases, it is necessary to evaluate the relation cost-benefit before applying the treatment.
Points 2 and 3 of that resolution increase controversy, both because of the small number of cases in controlled studies with parasitologic and serologic cure criteria that give sustained evidences of the benefits of tripanomicida therapy (points 2) and the few evidences of the therapeutic efficiency in grown ups with consistent results (points 3). Thus 3 deserves more consideration and debate in scientific institutions and forum, to generate criteria with foundations supporting them.
Brazil adopted a position similar to that of Argentina, recommending treatment of Chagas in sharp, latent and chronic phases, in patients that do not present severe symptons of cardiopaties or digestive problems .
Some investigators [51-52-53] suggest treatment in adults in chronic phase, maintaining that it gives the patient the probability of preventing or diminish the incidence of cardiopaties or even stop its evolution, decreasing morbimortality in patients with cardiopaties. It would be necessary to make a difference between 2 kinds of patients: those living in endemic areas (without vectorial controls) and urban patients (migrations to cities in endemic areas) because they need different strategies of treatment. What would happen with a chronic Chagas patient if treated with tripanomicida drugs.
Although the parasite is being erradicated, are we really stopping the autoinmune processes that cause damages in miocardic texture? This is a question that requires answers.
Several authors [49-54-55] do not impulse the application of the treatment in sharp phase patients because of the low possibilities of parasitological and serological cure, with doubtful clinic benefits in the long run and colateral intense effects suffered by patients in sharp phase of the illness living in endemic areas . It is also sustained that the evaluation of the efficiency of the treatment is very complex, as the infection itself .
Nowadays the rules of diagnostic and/or therapeutic behaviours are elaborated in function of Medicine Based on Evidences (MBE) ; it would be necessary to evaluate according to the knowledges we have, the results related to the application of specific treatment of Chagas during the chronic phase in grown ups.
This question should be answered through the advices of MBE, thanks to definite and indisputable evidences, observed in pathologies like those we now analyze (besides the information we have without definite sustain), to suggest effective therapeutic strategies.
The development of meta-analytical techniques contributes to clarify concepts, and makes it easier the communication of information among professionals with the creation of data base and access to bibliography about recent clinic investigation thanks to Internet, what allows us to take decisions with the base of scientifically demonstrated knowledges.
It is also important to make use of studies containing description of clinic and methodologic aspects about the evolution of morbimortality  and the importance of the production of scientific information with sustained evidences, through the making of studies with experimental designs that include the registry of clinic evolution of the illness (cure criteria), testing the traditional agents or maybe some new ones.
Villar J.C. and Col.  recently contributed with new meta-analysis techniques, that allow evaluation of effectiveness of different tripanomicida drugs in patients infected by T. Cruzi without evidences of cardiac damage with results of reduction of titles of anticorps and parasitemia, statistically significant for the studied proofs. This analysis was made through the study of registered works on Internet data base. There were included 1306 studies and only 5 of them [31,47,61,62,63] of a number of 756 people had the established conditions for inclusion criteria.
The rest lacked information related to methodologic aspects and omitted clinic aspects of the illness as cure criteria in the evaluation of the clinic efficiency of these agents. It's relevant nowadays with actual knowledges about specific therapy of chronic Chagas, because of the importance given to the evaluation of the clinic results of the different studies related to the efficiency evaluation both in latent and chronic phases of the illness.
Those promoting the application of treatment in chronic
phase  maintained that the patient has to
receive ethiologic treatment with Benznidazol because:
1) If Benznidazol is able to cure the sharp infection.
2) Is able to cure recent chronic illness (children and teen agers) similar to sharp cases.
3) Is able to cure in low percentages the chronic long lasting illness.
4) Has a suppressive effect of parasitemia in the long lasting chronic illness, with a possible favourable evolution.
5) In daily clinic practice, it has to be the professional's option , in front of a 25 years old patient, woman with children that discovered recently her illness with initial cardiopaty.
Conscious of the stated problems that gave origin to the controversies originated in the last years we think, as scientific institution, that it is convenient to remark some aspects of the problem: in the 1st. place, we have to revise the criteria to evaluate cure; this is a particularly complex aspect that offers difficulties in relation to clinic, serologic and parasitological aspects.
The application of these criteria is determined by an uncertainty in the particular phisiopatogeny of the illness, in which factors caused by the presence of the parasite involve enchained answers, such as: immune answer, autoimmunity phenomena, inflammatory reaction, deposits of complex antigenics, tisular damage. All of them with their consequent clinic manifestations that appear after long periods of time. The evaluation of these alterations can be the most difficult.
In relation to the parasitological cure criteria, "the cure of the patient" establishes as a supposition the elimination of the parasite, not only from the blood but also from the textures, fact that can't be confirmed in human beings. The parasitological methods (Xenodiagnosis) in chronic phase of the illness, just provide a sensitiveness of about 50%, similar to the hemoculture method.
The use of molecular biology methods (PCR) is seen as an ideal tool to measure parasitemia, specially in patients in chronic phase; anyway, the obtained results and the high costs, do not allow its systematic application.
The use of complementary methods has to exceed the traditional ECG and Rx, to use different methods designated to evaluate disorders of rhythm and registers of continuous ECG (Holter 24 hours of 3 channels), the variation of cardiac frequency (VFC) and the Late Ventricular Potential (PTV), and the morphological and functional systolic and diastolic evaluation of the left ventricle by means of studies with Cardiac Ecodoppler, elements that allow us to check patients before, during and after treatment. It seems to be important to add studies that observe the digestive function ,and tests that allow the observation of SNA.
It's important to remark aspects that must be considered before stating treatment in infected patients in chronic phase, such as to be sure that the patient is not living in endemic areas, and if he is, to maintain the house under entomologic control. It is also important to consider age, due in particular to the toxics of available drugs, with secondary effects which are more frequent in grown up patients; as we have already established, these effects increase proportionally with age.
The characteristics of complications can become severe (hepatopaties-Steve-Johnson) and last even after the end of treatment; it is also important the previous evaluation of the patient's health and be sure that periodical controls will be possible during the treatment.
All these methods or tests allow us to define clearly the basal profile of the patient with the object of judging in the future, through studies, the appearance of indicators revealing the beginning of pathology. We consider important to debate this problem to try to reach to scientific conclusions. The Chagas Committee has organized multicentric national studies to try to answer questions that Chagas states through the elaboration of planned studies following the rules that the scientific method establishes, to produce valid and reliable information.
Among the registries proposed by Chagas Committee and presented
in its Internet site, appear:
"Therapeutic Efficiency with Benznidazol in the Latent Phase of Chagas Illness", whose objectives are :
1. The use of diagnosis techniques based on methods of molecular biology.
It has been planned with non controlled designs because it had to be taken into consideration by the Bioethic Committee, as there are national rules that indicate the use in children and grown ups, and we weren't able to find scientific works to refuse them. This study with periodical controls during 4 years uses as cure criteria the following parameters: parasitologic, serologic and clinic, as an evidence to value the evolution of the illness with the recommendations of MBE.
Anticipating to the meta analysis results  the registry of relative study about the efficiency proposed by the Chagas Committee (actually standing in the Chagas Center and Regional Pathology "Dr. Humberto Lugones". Santiago del Estero, with 90 patients) states variables of observation that will serve to evaluate aspects of the clinic evolution of the illness.
We conclude that we have to produce reliable scientific information through multicentric studies to put light in many dark points of the subject to offer new rules clearly based. It is important to go on searching new drugs for the treatment of the illness with the requirements stated by WHO  - Meeting of the development of tripanomicida compounds for the sterilization of blood -UNDP/WB/TDR-Geneve) to define an ideal drug that allows: to obtain the parasitological cure in sharp and chronic cases, to obtain effectiveness in one or several dosis, to be accessible for patients because of its low cost, do not present colateral or teratogenic effects, do not need hospitalization for its treatment and do not induce resistance.
Multicentric works are available from July 2002 in FAC Web and were well received during their presentation in the XX Chagas Symposium, Cardiology National Congress 2001 and during the Continuous Education Forum.
1. Censo Poblacional 1990.
2. Cerisola J, Ravinovich A, Alvarez J, y Col.: Enfermedad de Chagas y transfusiones de sangre. Bol. Of. Sanit. Panam. 73: 203, 1072.
3. Segura EL, Pérez A, Yanosvsky JF y Col.: Disminución en la prevalencia de la infección por T. Cruzi. Enfermedad de Chagas en hombres jóvenes de la Argentina. Bol. Of. Sanit. Panam 1986; 100: 493.
4. Becker D, Del Prado C, Manzullo E y Col.: Un análisis del mal de Chagas. La Nación, Argentina, 30 junio 1987; 14-15.
5. Esquivel ML, Segura EL: Estimación del número de infectados chagásicos en la Argentina. Medicina 1994; 54: 91-92.
6. Cerisola JA, Rohweder R, Segura E y Col.:El Xenodiagnóstico: Normatización, utilidad. Publicación de la Secretaria de Salud Publica Ministerio de Bienestar Social. 1974; Bs. As., Argentina.
7. Stoppani A: Quimioterapia de la Enfermedad de Chagas. Medicina 1999: (sup. II):147-165.
8. Mazza S, Cossio R, Zucardi R: El Primer casos agudos de Enfermedad de Chagas comprobado en Tucumán y su tratamiento con Bayer 7602. Misión Estudios Patolog. Reg. Arg. 1937; 32: 2-18.
9. Tratamiento etiológico de la enfermedad de Chagas- Conclusiones de una Consulta técnica. OPS-OMS. Fundación Oswaldo Cruz. Rio de Janeiro, Brasil, 23-25 abril de 1998.
10. Cerisola JA: Chemotherapy of Chagas infection in man. Scientifc Publication PAHO 1977; N 347.
11. Lugones HS: Tratamiento de la Enfermedad de Chagas con ROO7 1051. Congreso Internacional de Pediatría. Bs. As. 1974.
12. Lugones HS, Ledesma OS y Col.: Preliminary Results Of The Anti T. Cruzi Activity of RO 1051 in man. III Congreso Internacional de Parasitología. Alemania 1974.
13. Barclay CA, Lugones HS y Col.: Resultados de la Actividad Anti Trypanosoma Cruzi del Benznidazol en el hombre. Actas VI Congreso Latinoamericano de Farmacología. Bs. As. 1976.
14. Lugones HS.: Aspectos Farmacológicos y Resultados Terapéuticos del Benznidazol en el tratamiento de la Infección Chagasica. Prensa Médica Argentina 1978; 65: 239.
15. Lugones HS.:Tratamiento de la Enfermedad de Chagas Aguda con Benznidazol. Revista Laboratorio Roche 1978; 1: 9.
16. Lugones HS.: Actualización terapéutica. Tratamiento de la Enfermedad de Chagas Agudo en Niños. Pediatría 1978; 2: 103-105.
17. Ledesma OS: Manifestaciones Neurológicas. Meningoencefalítis Chagásica Aguda. Congreso Argentino de Protozoología. Córdoba. 1984.
18. Lugones HS: Tratamiento de la Enfermedad de Chagas Aguda con Nifurtimox. Simposio Internacional de la Enfermedad de Chagas, Bs. As., 1979.
19. Rivarola W, Barbieri GP, Ledesma OS y Col.: Enfermedad de Chagas: Efecto de Prometazina Sobre Tripomastigostes en Sangre de Pacientes Con Infección Aguda. Xº Jornadas Científicas Sociedad de Biología de Córdoba, 1995.
20. Barclay CA, Cerisola JA, Lugones H y Col.:Aspectos farmacológicos y resultados terapéuticos del Benznidazol en el tratamiento de la infección chagásica. La Prensa Medica 1978; 65: 239-244.
21. Blanco S, Spilman C, Zarate J y Col.: Tratamiento y seguimiento de 147 niños de 1 a 14 años, infectados por T. cruzi en el área rural del departamento Pellegrini, en vigilancia entomológica. Sgo. del Estero, Argentina. Medicina 1997; 57: Sup. III 43-44.
22. Cancado R,: Terapéutica especifica. En Clínica e Terapéutica da Doenca de Chagas. Uma aborgagen practica para o clínico general. Pinto Días J, Rodrigues Coura J, Ed. Fiocruz 1997: 178.
23. Cichero JA, Segura E, Quatrochi JC.: Evolución Clínico Parasitología y tolerancia a la droga de 33 niños con infección Chagásica crónica tratados con Bay 2502. Bol. Chil. Parasitol 1969; 24: 59-62.
24. De Andrade ALS, Zicker F, De Oliveira RM y Col.: Randomized trial of efficacy of Benznidazol in treatment of early trypanosome Cruzi infection. The Lancet 1996; 348: 1407-1413.
25. Del Barco M, Striger M, Arias E y Col.: Repuesta al tratamiento en niños con infección Chagasica crónica. Medicina 1993; 53: (Sup. I) 78.
26. Fabro D, Arias E, Streiger M y Col.: Infectados chagásicos en fase indeterminada con mas de 15 años de seguimiento- Evaluación de la quimioterapia especifica. Medicina 1997; 57 (Sup. III): 42-13.
27. Ferreira HO: Tratamiento da forma indeterminada da doenca de Chagas com Nifurtimox o Benznidazol. Rev Soc Bras Med. Trop 1990; 23: 209.
28. Lugones H: Actualización terapéutica. Tratamiento de la enfermedad de Chagas aguda en niños. Pediatría 1978; 2: 103-105.
29. Moya PR, Paolasso RD, Blanco S: Tratamiento de la Enfermedad de Chagas con Nifurtimox durante los primeros meses de vida. Medicina 1985; 45: 553-558.
30. Viotti R, Vigliano C: Chronic Chagasic cardiomyopathy. Clinic and serologic evolution with and without Benznidazol in log term folow up. XVIII. Congreso Argentino de Cardiología. Bs. As. 1999.
31. Sosa Estani S, Segura EL, Ruiz M y Col.: Efficacy of chemotherapy with Benznidazole in children in the indeterminate phase of chagas' desease. Am J. Trop. Med. Hyg 1998; 59: (4) 526-529.
32. Cancado, J.R.: Terapéutica específica, en Pinto, Dias JC, Rodríguez Coura J. (Ed.) Clinica e terapeutica da doenca de Chagas. Rio de Janeiro, Brasil: Editora FIOCRUZ, 323-351, 1997.
33. Solari A, Ortiz S, Soto A, y Col.: Treatment of Trypanosoma cruzi-infected children with nifurtimox: a 3 year follow-up by PCR Molecular and Cellular Biology Programme, and Parasitology Programme, Biomedical Sciences Institute, Faculty of Mediciene, University of Chile, Cailla 70086, Santiago 7, Chile.
34. Jones EM, Coley DG, Tostes S, y Col.: Amplification of de T cruzi DNA sequence from inflamatory lesions in human chagasic cardiomyophaty. Am J. Trop Med Hyg 1993; 48: 348-57.
35. Cunha-Neto E. Repensando la patogenia de la cardiopatia cronica chagásica en el final del milenio. Editorial, Medicine (Bs As) 1999; 59: 496-500.
36. Díaz C, Beloscar J, Pellizon D.: Anticuerpos hacia la proteína de stres térmica HPS de G5 Kd en pacientes con Miocardiopatia chagásica crónica. Resumen XX congreso Nacional de Cardiología, Córdoba, 2001.
37. Resolución Secretaria de Programas de Salud, Ministerio de Salud y Acción Social de la Nación. Norma Nº 28/99. Normas para atención médica del Infectado Chagásico. Ministerio de salud y Acción Social y COFESA, Noviembre de 1983, Bs. As., Argentina.
38. Korettli AV, Cancao JR, Brener Z y Col.: Effect of especific chemotherapy on the levels of lytic antibodies in chagas disease. Trans R. Soc. Med. Hyg. 1982; 76: 334-340.
39. Cancado R.:- Boletín Chileno de Parasicología 1969; 24: 1-4.
40. Rassi, A., Luquetti, A.O. Therapy of Chagas Disease. In: Wendel, S., Brener, l., Camargo, M.E., Rassi, A. (Ed.) Chagas Disease (American Trypanosomiasis), its impact on Transfusion and Clinical Medicine, sao Paulo: Sociedade Brasileira de Hematologia e Hemoterapia pp 237-247, 1992.
41. Fragata, Fo. A.A., Luquetti, A.O., Prata, A. y Col.: Tratamento etiológico da doenca de Chagas. Ed. Fundacao Nacional de Saúde, Brasília, 2da. edicao. p 32, 1997.
42. Luquetti, A.O. Etiological treatment for Chagas disease. Parasit. Today,13: 127-128, 1997.
43. Zicker, F., Smith, P.G., Luquetti, A.O., Oliveira, O.S.: Mass screening for Trypanosoma cruzi infections using the immunofluorescence, ELISA and haemagglutination tests on serum samples and on blood eluates from filter-paper. Bull. World Health Org. 68: 465- 471, 1990.
44. Reyes, M.B., Luquetti, A.O., Rassi, A. y Col.: Long lasting IgM and IgG reactivities against Trypanosoma cruzi antigens in human cases of Chagas' disease. Anal. Asoc. Química Argentina 81: 101-110, 1993.
45. Criterios para la atención al infectado chagásico- Instituto Nacuioanla de Chagas Dr. Mario Fatala Chaben- Servicio Nacional de Chagas- Secretaria de Salud de la Nacioa, Bs As, junio 1995
46. WHO: Control de Chagas Desease. Who. Techni Rep Serv. 1991; Nro. 811, Genova.
47. Sgambatti de Andrade AL, Zicker F, de Oliveira RM y Col.: Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma Cruzi infection. Lancet 348, 1407-1413. 1996.
48. Manual para la atención del paciente Infectado Chagasico. Ministerio de Salud y Accion Social de la Nación. 1998.
49. Reyes M: Simposio sobre Enfermedad de Chagas, XX CONGRESO NACIONAL DE CARDIOLOGIA, Córdoba, 28/4-1/5 2001.
50. Britto C, Cardozo A, Silveira C y Col.: Problemática de Enfermedad de Chagas, Simposio Internacional, Academia Nacional de Medicina 1999. Medicina 1999; 59 (supl.II): 176-178.
51. Cancado R.: Simposio sobre Enfermedad de Chagas, XX CONGRESO NACIONAL DE CARDIOLOGIA, Córdoba, 28/4-1/5 2001.
52. Gallerano R, Sosa R.: Resultados de un estudio a largo plazo con drogas antiparasitarias en infectados chagásicos crónicos. Rev Fed Arg Cardio1 2001; 50: 289-296.
53. Viotti R, Vigliano C, Armenti H. y Col.: Treatmente of chronic Chagas'disease with benznidazole: Clinical and serologic evolution of patients with long-term follow-up. Am Heart J 1994; 127: 151-162.
54. Manzullo E: Simposio sobre Enfermedad de Chagas, XX CONGRESO NACIONAL DE CARDIOLOGIA, Córdoba, 28/4-1/5 2001.
55. Pinto Dias JC: Foro de Educación Continua en Cardiología, Enfermedad de Chagas, FAC, Octubre-9, 2000.
56. Cataleoti F, Acquatella H, Comparación de mortalidad durante el seguimiento por 5 años en sujetos con infeccion de Chagas crónico con y sin tratamiento con benznidazol. 1º Virtual Congreso de Cardiología por Internet Sep 2001).
57. Sosa Estani S.: Foro de Educación Continua en Cardiología, Enfermedad de Chagas FAC, agosto 2001.
58. Doval H, Tajer C: Evidencias en Cardiología. GEDIC. Imprecolor SA. Bs. As. Nov 2000, pag XXIV.
59. Neto JM.: Simposio sobre Enfermedad de Chagas, XX CONGRESO NACIONAL DE CARDIOLOGIA, Córdoba, 28/4-1/5 2001.
60. Villar J.C., Villar L.A., Marin-Neto J.A. y Col.: Efficacy of Trypanocidal Therapy for Chronic Asymptomatic Trypanosoma Cruzi Infection. A Meta-Analysis. Segundo Congreso Virtual de Cardiología (Congreso Nacional de Cardiología realizado por Internet), organizado por la Federación Argentina de Cardiologia, sep-nov de 2001.
61. Apt W, Aguilera X, Arribada A, y Col.: Treatment of chronic Chagas' disease with itraconazole and a1lopurinol. Am J Trop Med Hyg. 1998;59:133-8.
62. Coura JR, de Abreu LL, Faraco Willcox HP y Col.: Estudo comparativo controlado com emprego de Benznidazole, Nifurtimox e placebo, na forma cronica da doenca de Chagas, em uma área de campo com transmissao o interrumpida. I. Ava1iacao preliminar. Rev Soc Bras Med Trop. 1997;30: 139-44.
63. Gianella A, Holzman A, Lihoshi N Y Col.: Eficacia del Allopurinol en la enfermedad de Chagas crónica. Resultados del estudio realizado en Santa Cruz, Bolivia. Bol Cientif CENETROP 16, 25-30. 1997.
64. Cancado R- Simposio sobre Enfermedad de Chagas, XX CONGRESO NACIONAL DE CARDIOLOGIA, Córdoba, 28/4-1/5 2001.
65. Macedo VO, Silveira CA: Perspectivas da terapeutica especifica na doenca de Chagas. Experiencias na forma indeterminada. Rev Soc Bras Med Trop 20(supl II):M24-M26
66. Pagina del Comité de Chagas de FAC, en el sitio de Federación Argentina de Cardiología en Internet. www.fac.org.ar/comites/multicentricos
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