Use of the polymerase chain reaction (PCR) for early evaluation of etiological treatment in young adults, chronically infected with Trypanosoma cruzi

Foi realizado o tratamento etiológico com benznidazol, no Estado de Salta, Argentina, em 14 pacientes infectados crônicos por Trypanosoma cruzi, de 18 a 30 anos de idade, com Reação em Cadeia da Polimerase (PCR) positiva. Um grupo controle de cinco pacientes, da mesma idade, também com PCR positiva, não recebeu tratamento. O seguimento após tratamento foi realizado com PCR e sorologia convencional. Após 6 meses de tratamento foi observada negativização da PCR de 14/16 (85,7por cento) nos pacientes tratados versus 20por cento no grupo controle (p=0,001). A sorologia foi positiva em todos os pacientes depois do tratamento. Os resultados da PCR pós-tratamento, podem ser um indício de cura no tratamento de infectados chagásicos crônicos, adultos jovens.

Comparative efficacies of TAK-187, a long-lasting ergosterol biosynthesis inhibitor, and benznidazole in preventing cardiac damage in a murine model of Chagas' disease.

We carried out a comparative study of benznidazole and TAK-187, a long-lasting ergosterol biosynthesis inhibitor, with a murine model of Chagas' disease. The results indicated that TAK-187 was more effective than benznidazole in preventing Trypanosoma cruzi-induced cardiac damage in experimental animals.

Early diagnosis of congenital Trypanosoma cruzi infection using PCR, hemoculture, and capillary concentration, as compared with delayed serology.

Congenital Trypanosoma cruzi infection is a highly pathogenic and underreported condition. Early recognition is essential for effective treatment. Umbilical chord blood from newborns (n = 302) to infected mothers was analyzed with microhematocrit, hemoculture, and PCR methods. Each subject was then followed serologically. In calibrated suspensions of T. cruzi in blood, the sensitivity of PCR was 27-fold higher than hemoculture. However, this advantage was not reflected during routine testing of samples from maternities, partly because of the uneven distribution of few parasites in small samples. Levels of detection of congenital infection were 2.9% (8/272) for microhematocrit, 6.3% (18/287) for hemoculture, 6.4% (15/235) for PCR, and 8.9% (27/302) for cumulated results. Evaluation against the standard of delayed serology indicates that the regular application of PCR, hemoculture, and microhematocrit to blood samples allows the rapid detection of about 90% of the congenitally infected newborns, in samples that can be obtained before the mother and child leave the maternity ward.

Relationship between long-term resistance to Trypanosoma cruzi and latent infection, examined by antibody production and polymerase chain reaction in mice.

Trypanosoma cruzi infections persist for the lifetime of humans and laboratory animals as either latent or pathogenic parasitism. Mice inoculated with a nonpathogenic, attenuated strain (TCC) display resistance against virulent challenge, with a strong control of parasitemia and protection against tissue lesions for more than 12 mo. Three main approaches were used to test whether protection by TCC inocula is based on a latent infection or on a "sterile" immunological memory: curative Benznidazole (Bzl) treatment, serological reactions, and detection of infection by polymerase chain reaction (PCR). If resistance is maintained in the absence of infection, it should not be reduced by Bzl treatment and TCC-inoculated animals should not maintain long-term serological or PCR reactivity. The Bzl treatment after TCC inoculations did not reduce, after periods of up to 420 days, TCC-induced resistance to challenge. But TCC inocula given during Bzl treatment conferred short-term, but not long-term. protection. Maintenance of high antibody levels and protection were better in the virulent Tulahuen (TUL) strain than in the attenuated TCC strain infections, and trypomastigote inocula of either strain were better inducers of antibodies and resistance than epimastigotes. PCR detection of T. cruzi DNA was positive in almost all TUL strain-inoculated animals and negative in immunocompetent animals inoculated with TCC epimastigotes, although high numbers of TCC trypomastigotes produced persistent PCR signals of infection in newborn BALB mice. Thus, 2 polar models were developed, where latent infection by TCC was either demonstrated or excluded. In both, resistance to virulent challenge was maintained during long periods. But late declination of antibody titers (>200 days) and resistance to challenge (>350 days) was observed in animals displaying clearance of all signals of infection.

Studies on the virulence and attenuation of Trypanosoma cruzi using immunodeficient animals

Tissue invasion and pathology by Trypanosoma cruzi result from an interaction between parasite virulence and host immunity. Successive in vivo generations of the parasite select populations with increasing ability to invade the host. Conversely, prolonged in vitro selection of the parasite produces attenuated sublines with low infectivity for mammals. One such subline (TCC clone) has been extensively used in our laboratory as experimental vaccine and tested in comparative experiments with its virulent ancestor (TUL). The experiments here reviewed aimed at the use of immunodeficient mice for testing the infectivity of TCC parasites. It has not been possible to obtain virulent, revertant sublines by prolonged passaged in such mice

Protección inmunológica contra la enfermedad de Chagas: efectos independientes sobre infección, diseminación y lesiones por Trypanosoma cruzi / Immunological protection against Chagas' disease: independent effects upon infection, dissemination and lesions by Trypanosoma cruzi

Una cepa atenuada de Trypanosoma cruzi (TCC) ejerce efectos inmunizantes contra parásitos jomólogos virulentos. La titulación de las dosis de TCC que son infecciosas o protectoras revela un rango amplio de dosis inmunizantes para los epimastigotes y capacidad de infección subpatente para tripomastigotes a dosis altas. Cuando se investiga la presencia de parásitos en animales inmunizados y luego inoculados con T. cruzi virulentos, a medida que se aumenta la sensibilidad de detección, se pueden revelar diferentes níveles de resistencia. Estos varían desde la total prevención de la infección en muy pocos animales hasta la simple reducción de mortalidad y parasitemias altas. Con 4 tipos de vacunas experimentales, 2 de parásitos inactivados y 2 de parásitos atenuados, se estudió independientemente la potenciación de cada nível de resistencia. Todas fortalecieron significativamente un tipo de resistencia muy aparente pero incompleto. Ninguna produjo cambios significativos en cuanto al rechazo total de pequeñas dosis de parásitos virulentos. Aunque estos niveles de resistencia no parecen utilizables para la prevención de la infección humana, es concebible que se puedan utilizar para interferir el ciclo doméstico de transmisión del parásito. Una evidencia preliminar de esta posibilidad se ha obtenido en el campo mediante la vacunación de cuises (Cavia porcellus) contra la infección natural por T. cruzi con vacunas experimentales atenuadas o inactivadas

Protección inmunológica contra la enfermedad de Chagas: efectos independientes sobre infección, diseminación y lesiones por Trypanosoma cruzi / Immunological protection against Chagas disease: independent effects upon infection, dissemination and lesions by Trypanosoma cruzi

Una cepa atenuada de Trypanosoma cruzi (TCC) ejerce efectos inmunizantes contra parásitos jomólogos virulentos. La titulación de las dosis de TCC que son infecciosas o protectoras revela un rango amplio de dosis inmunizantes para los epimastigotes y capacidad de infección subpatente para tripomastigotes a dosis altas. Cuando se investiga la presencia de parásitos en animales inmunizados y luego inoculados con T. cruzi virulentos, a medida que se aumenta la sensibilidad de detección, se pueden revelar diferentes níveles de resistencia. Estos varían desde la total prevención de la infección en muy pocos animales hasta la simple reducción de mortalidad y parasitemias altas. Con 4 tipos de vacunas experimentales, 2 de parásitos inactivados y 2 de parásitos atenuados, se estudió independientemente la potenciación de cada nível de resistencia. Todas fortalecieron significativamente un tipo de resistencia muy aparente pero incompleto. Ninguna produjo cambios significativos en cuanto al rechazo total de pequeñas dosis de parásitos virulentos. Aunque estos niveles de resistencia no parecen utilizables para la prevención de la infección humana, es concebible que se puedan utilizar para interferir el ciclo doméstico de transmisión del parásito. Una evidencia preliminar de esta posibilidad se ha obtenido en el campo mediante la vacunación de cuises (Cavia porcellus) contra la infección natural por T. cruzi con vacunas experimentales atenuadas o inactivadas (AU)