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%.
"cruzi response after etiological treatment. Nevertheless, in pediatric patients initiating therapy at the early chronic stage of infection, negative seroconversion occurs several years after treatment , therefore requiring long-term follow-up. Our present findings suggest that the BZ-dependent decline of Anti-M2R AAb and IFN-γ levels might provide a surrogate indicator of early therapeutic success in T. cruzi-infected children. "
[Show abstract][Hide abstract] ABSTRACT: The presence of autoantibodies with adrenergic and cholinergic activity, capable of triggering neurotransmitter receptor-mediated effects, has been associated with pathogenesis in T. cruzi-infected hosts. The goal of this study was to investigate the production of anti-M2 muscarinic receptor autoantibodies (Anti-M2R AAbs) as well as the IFN-γ profile in children at the early stage of Chagas disease, and to examine whether trypanocidal chemotherapy with benzonidazole (BZ) could modify both response patterns.
This study comprised 30 T. cruzi-infected children (mean age: 13.8 years) and 19 uninfected controls (mean age: 12.7 years). Infected patients were treated with BZ and followed-up. Blood samples collected at diagnosis-T0, end of treatment-T1, and six months later-T2 were analysed by ELISA for detection of Anti-M2R AAbs and circulating levels of IFN-γ.
At T0, anti-M2R AAbs were demonstrated in 56.7% of T. cruzi-infected patients, whereas uninfected controls were 100% negative. The average age of Anti-M2R AAbs(+) patients was higher than that from negative population. Infected children also displayed significantly stronger serum IFN-γ responses than controls. Upon BZ treatment, a significant linear decreasing trend in Anti-M2R AAb reactivity was recorded throughout the follow-up, with 29.7-88.1% decrease at T2. IFN-γ circulating levels also declined by T2.
Anti-M2R AAbs and IFN-γ raise early during chagasic infection in children and are downmodulated by BZ therapy. These findings reinforce the usefulness of early BZ treatment not only to eliminate the parasite but also to reduce potentially pathogenic immune responses.
PLoS ONE 10/2011; 6(10):e27133. DOI:10.1371/journal.pone.0027133 · 3.23 Impact Factor
[Show abstract][Hide abstract] 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(1):434-44. DOI:10.1196/annals.1381.046 · 4.38 Impact Factor
[Show abstract][Hide abstract] 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-VSφ) 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-VSφ 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.
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