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Biomedical subjects

S G Andrade

Publications and source records attributed to S G Andrade.

At least 37 records · Page 2Linked to original sources

Evaluation of chemotherapy with benznidazole and nifurtimox in mice infected with Trypanosoma cruzi strains of different types.

A test was made of the susceptibility of 30 strains of Trypanosoma cruzi to chemotherapy with nifurtimox (Bay 2502) and benznidazole (Ro 7-1051). The strains had previously been classified as type I, II, or III according to their morphobiological and isoenzymic characteristics. Three type I strains, 14 type II strains, and 13 type III strains were studied. Mice were infected with 2 x 10(5) blood forms of these parasites and treated for 90 days with benznidazole or nifurtimox. All the surviving mice were submitted to parasitological tests (direct parasitaemia, xenodiagnosis, inoculation in new-born mice, and haemoculture) and serological tests (indirect immunofluorescence). As the latter remained positive in about 80% of the parasitologically negative animals, the cure rates were based on the more reliable parasitological tests. Type I strains displayed high susceptibility, type II strains showed medium to high susceptibility, and type III strains were highly resistant to both drugs. The fact that a particular strain type, with its own level of susceptibility, usually predominates in a given geographical area may explain the contradictory results after chemotherapy from different endemic areas.

Animals↗

Patterns of resistance of inbred mice to Trypanosoma cruzi are determined by parasite strain.

Host response and parasite behavior of three different T. cruzi strains (I-Peruvian, II-21SF, III-Colombian) were investigated by evaluating the course of infection in six inbred strains of mice (A/J, AKR, C3H/He, BALB/c, C57BL/10, DBA/1). Resistance was evaluated in terms of the harmonic mean survival time and the infection was monitored by parasitemia, histopathology and immunological parameters (immunoglobulin subclass levels and antibody titers). All six mouse strains showed high susceptibility to the Peruvian strain (Type I). However, they displayed a different spectrum of susceptibility to Types II and III. Each T. cruzi strain maintained its basic features in the different mouse strains. Despite different maximum levels, the parasitemic curves were characteristic for each type of T. cruzi strain. There was a correlation between the degree of resistance of strains DBA and B10 and their high levels of IgG2a and IgG2b, as well as the presence of the H-2d haplotype, indicating that the genetic background of the mice is also important. The inflammatory process varied with each mouse strain and was correlated with the levels of IgG2a, with resistant mice showing predominance of neutrophilic infiltration with a rise in IgG2a. The susceptible strains responded with a mild inflammatory process with predominance of mononuclear cells. These data suggest that the parasite strain is the most important factor determining the resistance of the different mouse strains to infection with T. cruzi.

Animals↗

Damage and healing in the conducting tissue of the heart (an experimental study in dogs infected with Trypanosoma cruzi).

The consequences of acute inflammatory damage and chronic repair in the conducting system of the canine heart were observed after experimental Trypanosoma cruzi infection of young dogs. Acute infection lasted for 18-25 days and caused hyaline and lytic necrosis of the atrio-ventricular conducting fibres, the sinus node and the neurons in the cardiac para-sympathetic ganglia. Dogs that survived acute disease were examined after periods from 8 months to 3 years. Three main types of healing were found in the conducting system: fibrosis (diffuse and/or focal), sclero-atrophy and fatty infiltration. No signs of active chronic inflammation were present, although small focal residual accumulations of mononuclear cells were present in some animals. No evident electrocardiographic alterations were elicited by the presence of such cicatricial lesions. The animal model appears worthwhile for the study of the healing process in conducting tissue of the heart and for the better understanding of the asymptomatic phase of T. cruzi infection in man.

Acute Disease↗

Correlation between isoenzyme patterns and biological behaviour of different strains of Trypanosoma cruzi.

Three strains of Trypanosoma cruzi, used previously as prototypes for a classification based on the host-parasite relationships, as well as several stocks isolated from different geographical areas in Brazil, were submitted to isoenzymic analysis. Their isoenzyme patterns revealed a clear correlation with the biological data. The patterns obtained with the enzymes PGM, GPI, ASAT and ALAT permitted discrimination between each of the described types. Only one type was found in each geographical area studied, indicating a possible relationship between regional patterns and clinical presentation of Chagas' disease.

Alanine Transaminase↗

The influence of the strain of Trypanosoma cruzi in placental infections in mice.

Pregnant female mice were infected with Trypanosoma cruzi strains which differed according to several parameters and were classified as three different types. Mice were killed during either the acute or the chronic phase of infection. Animals' tissues and foetuses together with the placentas, were studied histopathologically. Clear cut differences were noted in the incidence of placental parasitism and in the localization of amastigotes in the vascular sinus of the placenta amongst the animals in the acute phase of the infection with different strains. No parasitism of the foetal tissues was seen. The incidence of placental parasitism reached 98% for the Colombian strain, 18.4% for the Peruvian strain, 17% for the Y strain and 13.2% for the Honorina strain (isolated from a woman that transmitted the infection to twins). The presence of parasites in the vascular part of the placenta was prominent with the Colombian strain and rare with the others. These experimental data seem to show that parasite strain plays a role in congenital T. cruzi infection.

Animals↗

Experimental Chagas' disease in dogs. A pathologic and ECG study of the chronic indeterminate phase of the infection.

Pathology of the chronic latent phase of Chagas' disease is poorly understood. In our experiment, nine dogs were inoculated with Trypanosoma cruzi and acute disease developed within 15 to 25 days, followed by a chronic asymptomatic period that varied from eight months to three years, at which time the animals were killed. Although ECG changes were minimal, all animals showed a mild focal chronic myocarditis, with a few microscopic foci of fibrosis. Focal or diffuse fibrosis, scleroatrophy, and fatty replacement were present in various parts of the conducting system, especially in the atrioventricular node, the distal portion of His' main bundle, and the initial portion of the right bundle. These lesions were considered to be sequelae from inflammation and necrosis during the acute phase of the infection. In addition to characterizing the lesions of the chronic indeterminate phase of Chagas' disease in the canine model, the present findings suggest that the lesions may be responsible for ECG changes that may appear in subjects with otherwise asymptomatic T cruzi infection.

Animals↗

Combined treatment with a nitrofuranic and a corticoid in experimental Chagas' disease in the dog.

In order to study the effect of combined treatment of Trypanosoma cruzi infection with a nitrofuranic drug and a corticoid, 27 dogs from three different litters infected with T. cruzi (12 SF strain) were randomly litter-paired in three experimental groups: animals infected and not treated; infected and treated with Bay 2502 (2-methyl-4-[5'nitrofurfurylideneamino]-tetrahydro-4H-1,4-thiazine-1,1-dioxine) (nifurtimox); infected and treated with nifurtimox plus betamethasone. While an enhanced myocarditis appeared in the animals treated with a nitrofuranic drug alone, inflammation was almost abolished when corticoid treatment was added. Both groups showed considerable intracellular parasite destruction. These changes were monitored by serial electrocardiograms and a final histopathologic study which included an investigation of the changes in the conducting tissue by serial sectioning. The survival period was prolonged in animals treated with the combination of the nitrofuranic drug and corticoid, and only in this group did some of the animals reach the chronic phase of the infection. Thus, the association of a nitrofuranic drug with a corticoid in the treatment of acute Chagas' disease produced parasite destruction and inhibited the inflammatory responses that are enhanced by such destruction

Animals↗

Histopathology of the conducting tissue of the heart in Chagas' myocarditis.

The conducting tissue of the heart was studied in 25 human cases of Chagas' myocarditis with a method which employs complete serial sections mounted on continuous transparent plastic tape. The pathological changes were correlated with electrocardiographic findings. The inflammation of the acute phase of Chagas' myocarditis, as seen in one single case, did not seem to interfere with conduction through the AV system. In chronic Chagas' myocarditis the conducting tissue showed extensive and variable changes: chronic inflammation, fibrosis, atrophy and fragmentation of specific fibers, extreme dilatation and tortuosity of veins, capillaries and lymphatics, fatty infiltration, and arterial medial and intimal fibrosis. A preferential involvement of the right bundle branch and the anterior fascicles of the left branch was observed and an excellent correlation with electrocardiographic abnormalities was found. There was also evidence presented that bundle branch block may be caused by disease proximal to the bundle branches. Complete AV block seemed to be the final result of the progressive inflammatory and degenerative changes involving the conduction system in chronic Chagas' myocarditis. Inflammation and fibrosis did also involve the sinoatrial node, Purkinje fibers, intracardiac nervous ganglia, and the contractile myocardium.

Acute Disease↗

Specific chemotherapy of Chagas disease: a comparison between the response in patients and experimental animals inoculated with the same strains.

Eleven strains of Trypanosoma cruzi were isolated from patients with Chagas disease in central Brazil by xenodiagnosis and inoculation into newborn mice. Biological characterization and isoenzyme analysis showed that 6 strains were type II (zymodeme 2) and 5 were type III (zymodeme 1). Patients were treated with benznidazole or benznidazole plus nifurtimox. Mice infected with each isolated strain were treated for comparison with the results obtained in the respective patient. Evaluation of cure of the patients was based on the indirect immunofluorescence test, complement fixation reaction and xenodiagnosis. For the mice, haemoculture, indirect immunofluorescence testing, xenodiagnosis and inoculation of blood into newborn mice were used. Tests were performed 3-6 months after the end of treatment. The cure rate was 66-100% in mice infected with type II strains and 0-9% in those infected with type III strains. The correlation between treatment results in patients and mice was 81.8% (9 of 11 cases). Type II strains were more susceptible to treatment, in contrast to type III strains which yielded the majority of therapeutic failures.

Adolescent↗

Investigation on the possibility of spontaneous cure of mice infected with different strains of Trypanosoma cruzi.

Seventy Swiss mice chronically infected with different strains of Trypanosoma cruzi, with persistently negative parasitemia on routine blood examination were parasitologically investigated to find out whether spontaneous cure occurred. Duration of infection varied from 90 to 250 days in the initial phase of this investigation. Parasitological tests consisted of daily direct blood examination performed during at least 25 days, followed by xenodiagnosis and subinoculation of blood into newborn mice. Mice that persisted negative were treated with Cyclophosphamide with one dose of 250 mg/kg of body weight and then investigated by direct blood examination, xenodiagnosis and subinoculation. A second dose of 250 mg/kg b. w. was given to the persistently negative mice. With one single exception, all mice showed positive parasitological tests in the different stages of the present investigation and we conclude that spontaneous cure did not occur in this group, which is representative of the chronic infection with different strains of T. cruzi.

Animals↗

Trypanosoma cruzi strains: behavior after passage into authoctonous or foreign species of traitomine (biological and biochemical patterns).

The behavior of T. cruzi strains from S. Felipe-BA (19 SF, 21 SF and 22 SF) classified as Type II Zymodeme 2, was investigated after passage through the authoctonous (P. megistus) and foreign vectors (T. infestans and R. prolixus). For each strain Swiss mice were infected: I--with blood forms (control); II--with metacyclic forms (MF) from P. megistus; III--with MF from T. infestans; IV--with MF from R. prolixus. Inocula: MF from the three species of triatomine, 60 to 120 days after feeding in infected mice, adjusted to 10(4). Biological behavior in mice (parasitemia, morphology, mortality, virulence and pathogenicity) after passage through triatomine was compared with data from the same strain in control mice. Isoenzymic electrophoresis (ASAT, ALAT, PGM, GPI) were also performed after culture into Warren medium. The three strains maintained the isoenzyme profiles (zymodeme 2), in the control groups and after passages through different species of triatomine. Biological characterization disclosed Type II strains patterns for all groups. An increased virulence was observed with the 22 SF strain isolated from P. megistus and T. infestans and higher levels of parasitemia and predominance of slender forms in mice inoculated with the 19 SF and 21 SF from these same species. Results indicate that the passage through the two species T. infestans and P. megistus had a positive influence on the virulence of the regional strains of S. Felipe, regardless of being autocthonous (P. megistus) or foreign to the area (T. infestans).

Animals↗