Congenital Chagas disease: experience in the Hospital de Niños, Ricardo Gutiérrez, Buenos Aires, Argentina
ABSTRACT Epidemiological, clinical, diagnostic, and therapeutic data from children who were born to mothers infected with T. cruzi who came to our hospital are presented. In addition, we exhibit the preliminary results of a technique that detects the anti F2/3 antibodies: these would be able to confirm the cure earlier than conventional serology. We also show the results of PCR diagnosis. Most of the mothers (76,1%) resided in Argentina, the rest were from Bolivia and Paraguay The median average age at diagnosis of the patients was 8,5 months (range 15 days-10 years). Out of 168 children, 64,98% were asymptomatic at diagnosis. The diagnosis criteria were: T. cruzi observation by microhematocrit technique in patients less than 7 month old. Two reactive serological tests in patients older than 8 months. A nifurtimox dose used in these patients was 10-13 mg/kg/d during 60 days. Although 31% presented side effects, none of them had to be dropped from the treatment. Cure criteria was conventional serology negativization. Of the patient population, we cured 87,2% of them, 98% of those under 3 years, and 100% of those who received treatment before age 8 months. We compared the time of negativization between conventional serology and anti F2/3 in 21 children. The latter were very useful to demonstrate (p>0,001) the success of the treatment, in those that started treatment after 8 months of age. PCR testing of a group of all patients, showed a diagnostic sensibility of 80,3% and a specificity of 97,8%.
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ABSTRACT: Chagas disease, caused by Trypanosoma cruzi, affects several million people in Central and South America. About 30% of chronic patients develop cardiomyopathy probably caused by parasite persistence and/or autoimmunity. While several cross-reactive antibodies generated during mammal T. cruzi infection have been described, very few cross-reactive T cells have been identified. We performed adoptive transfer experiments of T cells isolated from chronically infected mice. The results showed the generation of cardiac pathology in the absence of parasites. We also transferred cross-reactive SAPA-specific T cells and observed unspecific alterations in heart repolarization, cardiac inflammatory infiltration, and tissue damage.Annals of the New York Academy of Sciences 07/2007; 1107:434-44. DOI:10.1196/annals.1381.046 · 4.31 Impact Factor
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ABSTRACT: Chagas' disease, caused by the parasite Trypanosoma cruzi, remains the leading cause of cardiopathy in Latin America with about 12 million people infected. Classic clinical manifestations derive from infection of muscle cells leading to progressive cardiomyopathy, while some patients develop megacolon or megaesophagus. A very aggressive clinical course including fulminant meningoencephalitis has been reported in patients who contract Chagas' disease in the background of immunodeficiency. This includes patients with human immunodeficiency virus infection as well as patients receiving immunosuppressive therapy for organ transplant. Currently, only two drugs are approved for the treatment of Chagas' disease, nifurtimox and benznidazole. Both have significant limitations due to common and serious side effects as well as limited availability. A promising group of new drug leads for Chagas' disease is cysteine protease inhibitors targeting cruzain, the major protease of T. cruzi. The inhibitor N-methyl-Pip-F-homoF-vinyl sulfonyl phenyl (N-methyl-Pip-F-hF-VS phi) is in late-stage preclinical development. Therefore, the question arose as to whether protease inhibitors targeting cruzain would have efficacy in Chagas' disease occurring in the background of immunodeficiency. To address this question, we studied the course of infection in recombinase-deficient (Rag1(-/-)) and normal mice infected with T. cruzi. Infections localized to heart and skeletal muscle in untreated normal animals, while untreated Rag1(-/-) mice showed severe infection in all organs and predominantly in liver and spleen. Treatment with the dipeptide N-methyl-Pip-F-hF-VS phi rescued immunodeficient animals from lethal Chagas' infection. The majority (60 to 100%) of inhibitor-treated Rag1(-/-) mice had increased survival, negative PCR, and normal tissues by histopathological examination.Antimicrobial Agents and Chemotherapy 12/2007; 51(11):3932-9. DOI:10.1128/AAC.00436-07 · 4.45 Impact Factor
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ABSTRACT: Chagas disease is a neglected parasitic disease endemic in the Americas. It mainly affects impoverished populations and the acute phase of the infection mostly affects children. Many cases have also been detected in nonendemic countries as a result of recent migratory trends. The chronic phase is relatively asymptomatic, but 30% of patients with chronic infection eventually develop cardiac and digestive complications that commonly lead to death or disability. Only two drugs are available for the treatment of Chagas disease, benznidazole and nifurtimox. These drugs have been shown to be effective in the treatment of both acute and early chronic phases in children, but the pharmacokinetics of these drugs have never been studied in this population. We have set out to conduct a pharmacokinetics study of benznidazole in a pediatric population with Chagas disease. The results of this study are expected to allow better estimation of the optimal doses and schedule of pharmacotherapy for Chagas disease in children.Paediatric Drugs 01/2009; 11(1):33-37. DOI:10.2165/0148581-200911010-00012 · 1.72 Impact Factor