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1.
Transfusion ; 61(9): 2701-2709, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34240750

RESUMO

BACKGROUND: Chagas disease (CD) serological screening at blood banks is usually performed by a single highly sensitive serological assay, with chemiluminescent immunoassays (CLIAs) being the method of choice. CLIAs employ recombinant, fusion peptides and/or chimeric antigens that selectively capture anti-Trypanosoma cruzi antibodies. However, despite high sensitivity, the ability of these tests to identify CD-positive cases should be evaluated against T. cruzi strains circulating in specific locales. Herein, we used a latent class analysis (LCA) approach employing an array of four chimeric antigens to assess the diagnostic performance of the Liaison XL Murex Chagas CLIA for the detection of anti-T. cruzi IgG in serum samples. STUDY DESIGN AND METHODS: The study included a panel of 5014 serum samples collected from volunteer blood donors at the Hematology and Hemotherapy Foundation of the State of Bahia, submitted to anti-T. cruzi antibody detection using Liaison Chagas CLIA and LCA as a reference test in the absence of a gold standard. RESULTS: LCA classified 4993 samples as negative, while positivity for T. cruzi antibodies was predicted in 21 samples. Compared with LCA, CLIA demonstrated sensitivity and specificity of 76.2% and 99.5%, respectively, providing an overall accuracy of 99.4%. DISCUSSION: In blood banks lacking a de facto highly sensitive screening immunoassay, the low sensitivity offered by Liaison Chagas CLIA renders it unsuitable for standalone use in serological screening procedures for CD. Moreover, blood banks are encouraged to carefully assess the ability of diagnostic methods to identify local T. cruzi strains in circulation.


Assuntos
Doadores de Sangue , Segurança do Sangue , Doença de Chagas/diagnóstico , Trypanosoma cruzi/isolamento & purificação , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/sangue , Antígenos de Protozoários/imunologia , Doença de Chagas/sangue , Doença de Chagas/imunologia , Humanos , Medições Luminescentes , Trypanosoma cruzi/imunologia
3.
Trials ; 21(1): 328, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293523

RESUMO

BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.


Assuntos
Doença de Chagas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/isolamento & purificação , Adulto , Assistência ao Convalescente , Argentina/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/parasitologia , Doença Crônica , Colômbia/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Nitroimidazóis/farmacocinética , Carga Parasitária/estatística & dados numéricos , Segurança , Espanha/epidemiologia , Resultado do Tratamento , Tripanossomicidas/farmacocinética , Trypanosoma cruzi/genética
4.
Dis Markers ; 2020: 8074314, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184904

RESUMO

Chagas' disease is a neglected tropical disease caused by Trypanosoma cruzi which is endemic throughout Latin America and is spread by worldwide migration. Diagnosis is currently limited to serological and molecular techniques having variations regarding their sensitivity and specificity. This work was aimed at developing a new sensitive, applicable, and cost-effective molecular diagnosis technique for loop-mediated isothermal amplification-based detection of T. cruzi (Tc-LAMP). The results led to determining a highly homologous satellite repeat region (231 bp) among parasite strains as a molecular marker for diagnosing the disease. Tc-LAMP was performed correctly for detecting parasite DNA (5 fg for the CL Brener strain and 50 fg for the DM28, TcVI, and TcI strains). Assay results proved negative for DNA from 16 helminth species and 7 protozoa, including Leishmania spp. Tc-LAMP based on the highly repeated T. cruzi satellite region is thus proposed as an important alternative for diagnosing T. cruzi infection, overcoming other methods' limitations such as their analytic capability, speed, and requiring specialized equipment or highly trained personnel. Tc-LAMP could be easily adapted for point-of-care testing in areas having limited resources.


Assuntos
Doença de Chagas/diagnóstico , DNA Satélite/genética , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Trypanosoma cruzi/isolamento & purificação , DNA de Protozoário/genética , Marcadores Genéticos , Humanos , Técnicas de Diagnóstico Molecular/economia , Técnicas de Amplificação de Ácido Nucleico/economia , Testes Imediatos , Sensibilidade e Especificidade , Trypanosoma cruzi/genética
5.
Biochim Biophys Acta Mol Basis Dis ; 1866(5): 165689, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32001300

RESUMO

This review is a perspective on the history of Chagas disease, and it adopts a novel approach from literary studies, historical documents and the science and epidemiology of the nature of the disease. From this analysis, comes the review's working definition of the Contact Zone (CZ): "the space in which geographically and historically separated people come into contact with each other and establish long-lasting relationships, which usually involve coercive conditions, radical inequality and intolerable conflict." In the Patient-Physician CZ, we verified the triple transition phenomena: the American trypanosomiasis shifted from a rural, acute, and vectorial transmitted disease to an urban, chronic and non-vectorial disease. In the Academic CZ, we describe the original disagreements which denied the existence of the disease and the current controversies about pathogenic mechanisms and etiological treatment. From the News from Latin America, and in the Original CZ, we will review the evolution of different forms of transmission. As in any good story, research across broad disciplines is necessary to reveal historical perspectives, scientific approaches, and the epidemiology of the disease, which has a prequel of 9000 years and an open ending: thus, we explore across the Global CZ, with its multiple and unexpected actors.


Assuntos
Doença de Chagas/história , Erradicação de Doenças/organização & administração , Doenças Endêmicas/história , Doenças Negligenciadas/história , Trypanosoma cruzi/patogenicidade , Animais , Restos Mortais/parasitologia , Doença de Chagas/epidemiologia , Doença de Chagas/prevenção & controle , Doença de Chagas/transmissão , DNA de Protozoário/isolamento & purificação , Erradicação de Doenças/história , Erradicação de Doenças/tendências , Vetores de Doenças , Doenças Endêmicas/prevenção & controle , Antropologia Forense/história , Carga Global da Doença , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , Humanos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologia , Doenças Negligenciadas/prevenção & controle , Triatoma/parasitologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação
6.
Biochim Biophys Acta Mol Basis Dis ; 1866(5): 165691, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32006572

RESUMO

More than 110 years has passed since the first publications on Chagas disease, and it still urges the necessity of understanding it as a complex socioenvironmental issue in which components of diverse nature converge and interact beyond the biomedical and epidemiological aspects. The current scenarios of the issue, both rural and Latin American as urban and global, demand that the education on Chagas disease include all possible contexts: where there are insect vectors and where there are not; inside and outside Latin America; in rural, periurban, and urban areas; in formal and non-formal educational environments. We consider essential the requirement of both an integral approach that overcomes the biomedical aspect to include the multidimensionality of the issue and a dialogical educational perspective that allows individuals and communities to analyze, decide, and lead contextualized prevention and promotion actions regarding their health. In this study, we surveyed, described, and critically analyzed studies approaching the link education-Chagas disease in scientific publications from the last 15 years. We aimed at contributing methodological-theoretical elements to (re)think the development of educational research and experiences that truly help facing this issue. From the electronic search of scientific literature in 6 databases, we found 426 articles, out of which we selected 25. We incorporated 10 articles from other sources to this initial corpus and performed both qualitative and quantitative analyses over the total number [35] to characterize the studied works in general, focusing on the conceptions on the Chagas disease issue and the underlying health education approaches.


Assuntos
Doença de Chagas/prevenção & controle , Doenças Negligenciadas/prevenção & controle , Educação de Pacientes como Assunto , Triatoma/parasitologia , Trypanosoma cruzi/patogenicidade , Animais , Pesquisa Biomédica/estatística & dados numéricos , Doença de Chagas/epidemiologia , Doença de Chagas/parasitologia , Doença de Chagas/transmissão , Controle de Doenças Transmissíveis/economia , Controle de Doenças Transmissíveis/organização & administração , Erradicação de Doenças/economia , Erradicação de Doenças/organização & administração , Vetores de Doenças , Carga Global da Doença , Humanos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologia , Política , Publicações/estatística & dados numéricos , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação
7.
PLoS Negl Trop Dis ; 13(8): e0007668, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31465522

RESUMO

BACKGROUND: Evaluation of therapeutic response in chronic Chagas disease is a major challenge, due to prolonged persistence of Trypanosoma cruzi-specific antibodies, lack of sensitivity of parasitological tests, and need for long-term follow-up to observe negative seroconversion of conventional serological tests (CS). The objective of this study was to evaluate F2/3-ELISA serology, a promising early biomarker of therapeutic response, and T.cruzi Polymerase chain reaction (PCR) for T. cruzi Deoxyribonucleic acid (DNA), for neonatal diagnosis and evaluation of parasitemia after treatment. METHODS: Prospective cohort study, with three-year clinical, serological and parasitological follow-up of pediatric Chagas disease patients treated with benznidazole. Serology was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA), Indirect hemagglutination (IHA) and F2/3-ELISA; Parasitemia by microhematocrit (MH) and PCR. RESULTS: A cohort of 107 pediatric patients treated with benznidazole was enrolled in the study. ELISA and IHA were initially reactive in 100% of patients, F2/3-ELISA serology was reactive in 80% (86/107) and 91% (97/107) had detectable parasitemia. Seventy-six (71%) patients completed at least 36 months of serological follow up after treatment. Although a similar decreasing linear trend was observed for all serological tests, F2/3-ELISA presented earlier, age dependent, negative seroconversion compared to CS. All patients reaching undetectable CS titers had previously seroreverted by F2/3-ELISA. All patients with persistently decreasing antibody titers had negative PCRs throughout the follow up period. No new cardiological lesions were observed during the 3 years follow-up period. CONCLUSIONS: The data reported here, using CS, F2/3 ELISA and PCR provide support for the efficacy of benznidazole in congenital Chagas diseases. These results provide support for scaling up of screening, diagnosis and access to benznidazole treatment. TRIAL REGISTRATION: ClinicalTrials.gov 0028/04 in the Research Council, Secretary of Health Buenos Aires city Goberment.


Assuntos
Anticorpos Antiprotozoários/sangue , Antiprotozoários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/imunologia , Trypanosoma cruzi/imunologia , Adolescente , Formação de Anticorpos , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Nitroimidazóis/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
8.
PLoS One ; 14(1): e0210156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30615644

RESUMO

BACKGROUND: Despite the adoption of campaigns to interrupt the main vector and to detect Trypanosoma cruzi in blood banks, millions of people are still chronically infected; however, the prevalence data are limited, and the epidemiology of Chagas disease has not been systematically evaluated. This study aimed to estimate the prevalence of Chagas disease in Colombia. METHODS: A systematic literature review and meta-analysis was conducted to select all observational studies reporting the prevalence of Chagas disease in Colombia, based on serological diagnosis in participants of any age and published between January 2007 and November 2017. Pooled estimates and 95% confidence intervals (95% CIs) were calculated using random-effects models. In addition, the I2 statistic was calculated. RESULTS: The literature search yielded a total of 1,510 studies; sixteen articles with relevant prevalence data were included in the systematic review. Of these, only 12 articles were included for entry in the meta-analysis. The pooled prevalence of Chagas disease across studies was 2.0% (95% CI: 1.0-4.0). A high degree of heterogeneity was found among studies (I2 > 75%; p < 0.001). The publication bias was not statistically significant (Egger's test, p = 0.078). The highest pooled prevalences were found in the adult population (3.0%, 95% CI: 1.0-4.0), pregnant women (3.0%, 95% CI: 3.0-4.0) and the Orinoco region (7.0%, 95% CI: 2.2-12.6). CONCLUSIONS: The results indicate that the T. cruzi-infected population is aging, the adult population, pregnant women and that the Orinoco region (department of Casanare) have the highest prevalences. These results highlight the need to maintain screening and surveillance programs to identify people with chronic T. cruzi infections.


Assuntos
Doença de Chagas/epidemiologia , Vetores de Doenças , Complicações Parasitárias na Gravidez/epidemiologia , Trypanosoma cruzi/isolamento & purificação , Animais , Doença de Chagas/diagnóstico , Doença de Chagas/parasitologia , Doença de Chagas/prevenção & controle , Doença Crônica/epidemiologia , Doença Crônica/prevenção & controle , Colômbia/epidemiologia , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Programas de Rastreamento/organização & administração , Programas de Rastreamento/estatística & dados numéricos , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/prevenção & controle , Prevalência
9.
Am J Trop Med Hyg ; 98(6): 1733-1742, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29714163

RESUMO

Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.


Assuntos
Doença de Chagas/epidemiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Parasitárias na Gravidez/epidemiologia , Trypanosoma cruzi/isolamento & purificação , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Doença de Chagas/transmissão , Estudos de Coortes , Redução de Custos , Testes Diagnósticos de Rotina , Feminino , Humanos , Recém-Nascido , Programas de Rastreamento/economia , Morbidade , Mães , Triagem Neonatal/economia , Gravidez , Complicações Parasitárias na Gravidez/mortalidade , Complicações Parasitárias na Gravidez/parasitologia , Prevalência , Estados Unidos
10.
Clin Infect Dis ; 67(4): 519-524, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29438471

RESUMO

Background: Trypanosoma cruzi causes Chagas disease in the Americas. The outcome of infection ranges from lifelong asymptomatic status to severe disease. Relationship between T. cruzi lineage (TcI-TcVI) infection history and prognosis is not understood. We previously described peptide-based lineage-specific enzyme-linked immunosorbent assay (ELISA) with trypomastigote small surface antigen (TSSA). Methods: A novel rapid diagnostic test (RDT; Chagas Sero K-SeT) that incorporates a peptide that corresponds to the TSSA II/V/VI common epitope was developed and validated by comparison with ELISA. Patients from Bolivia and Peru, including individuals with varying cardiac pathology, and matched mothers and neonates, were then tested using Chagas Sero K-SeT. Results: Chagas Sero K-SeT and ELISA results, with a Bolivian subset of cardiac patients, mothers, and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) with class B (electrocardiogram suggestive of Chagas cardiomyopathy) and class C/D (decreased left ventricular ejection fraction; moderate/severe Chagas cardiomyopathy) revealed a statistically significant increase in Chagas Sero K-SeT reactivity with increasing severity (χ2 for trend, 7.39; P = .007). In Peru, Chagas Sero K-SeT detected the sporadic TcII/V/VI infections. Conclusions: We developed a low cost RDT that can replace ELISA for identification of TSSA II/V/VI immunoglobulin G. Most importantly, we show that response to this RDT is associated with severity of Chagas cardiomyopathy and thus may have prognostic value. Repeated challenge with T. cruzi infection may both exacerbate disease progression and boost the immune response to the TSSApep-II/V/VI epitope.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Testes Sorológicos/métodos , Índice de Gravidade de Doença , Trypanosoma cruzi/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Protozoários/imunologia , Bolívia , Ensaio de Imunoadsorção Enzimática , Feminino , Sangue Fetal/parasitologia , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Peru , Testes Sorológicos/economia , Adulto Jovem
11.
PLoS Negl Trop Dis ; 12(1): e0006222, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29364882

RESUMO

OBJECTIVE: We evaluated the effect of Trypanosoma cruzi infection on fertility, gestation outcome, and maternal-fetal transmission in guinea pigs (Cavia porcellus). METHODS: Animals were infected with T. cruzi H4 strain (TcI lineage) before gestation (IBG) or during gestation (IDG). Tissue and sera samples of dams and fetuses were obtained near parturition. RESULTS: All IBG and IDG dams were seropositive by two tests, and exhibited blood parasite load of 1.62±2.2 and 50.1±62 parasites/µl, respectively, by quantitative PCR. Histological evaluation showed muscle fiber degeneration and cellular necrosis in all infected dams. Parasite nests were not detected in infected dams by histology. However, qPCR analysis detected parasites-eq/g heart tissue of 153±104.7 and 169.3±129.4 in IBG and IDG dams, respectively. All fetuses of infected dams were positive for anti-parasite IgG antibodies and tissue parasites by qPCR, but presented a low level of tissue inflammatory infiltrate. Fetuses of IDG (vs. IBG) dams exhibited higher degree of muscle fiber degeneration and cellular necrosis in the heart and skeletal tissues. The placental tissue exhibited no inflammatory lesions and amastigote nests, yet parasites-eq/g of 381.2±34.3 and 79.2±84.9 were detected in IDG and IBG placentas, respectively. Fetal development was compromised, and evidenced by a decline in weight, crow-rump length, and abdominal width in both groups. CONCLUSIONS: T. cruzi TcI has a high capacity of congenital transmission even when it was inoculated at a very low dose before or during gestation. Tissue lesions, parasite load, and fetal under development provide evidence for high virulence of the parasite during pregnancy. Despite finding of high parasite burden by qPCR, placentas were protected from cellular damage. Our studies offer an experimental model to study the efficacy of vaccines and drugs against congenital transmission of T. cruzi. These results also call for T. cruzi screening in pregnant women and adequate follow up of the newborns in endemic areas.


Assuntos
Doença de Chagas/patologia , Doença de Chagas/transmissão , Transmissão Vertical de Doenças Infecciosas , Troca Materno-Fetal , Complicações Infecciosas na Gravidez/patologia , Trypanosoma cruzi/isolamento & purificação , Animais , Anticorpos Antiprotozoários/sangue , Modelos Animais de Doenças , Feminino , Cobaias , Histocitoquímica , Humanos , Imunoglobulina G/sangue , Carga Parasitária , Reação em Cadeia da Polimerase , Gravidez
12.
PLoS Negl Trop Dis ; 11(9): e0005929, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28945741

RESUMO

Four sesquiterpene lactones, mikanolide, deoxymikanolide, dihydromikanolide and scandenolide, were isolated by a bioassay-guided fractionation of Mikania variifolia and Mikania micrantha dichloromethane extracts. Mikanolide and deoxymikanolide were the major compounds in both extracts (2.2% and 0.4% for Mikania variifolia and 21.0% and 6.4% for Mikania micrantha respectively, calculated on extract dry weight). Mikanolide, deoxymikanolide and dihydromikanolide were active against Trypanosoma cruzi epimastigotes (50% inhibitory concentrations of 0.7, 0.08 and 2.5 µg/mL, for each compound respectively). These sesquiterpene lactones were also active against the bloodstream trypomastigotes (50% inhibitory concentrations for each compound were 2.1, 1.5 and 0.3 µg/mL, respectively) and against amastigotes (50% inhibitory concentrations for each compound were 4.5, 6.3 and 8.5 µg/mL, respectively). By contrast, scandenolide was not active on Trypanosoma cruzi. Besides, mikanolide and deoxymikanolide were also active on Leishmania braziliensis promastigotes (50% inhibitory concentrations of 5.1 and 11.5 µg/mL, respectively). The four sesquiterpene lactones were tested for their cytotoxicity on THP 1 cells. Deoxymikanolide presented the highest selectivity index for trypomastigotes (SI = 54) and amastigotes (SI = 12.5). In an in vivo model of Trypanosoma cruzi infection, deoxymikanolide was able to decrease the parasitemia and the weight loss associated to the acute phase of the parasite infection. More importantly, while 100% of control mice died by day 22 after receiving a lethal T. cruzi infection, 70% of deoxymikanolide-treated mice survived. We also observed that this compound increased TNF-α and IL-12 production by macrophages, which could contribute to control T. cruzi infection.


Assuntos
Lactonas/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Mikania/química , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Descoberta de Drogas , Interleucina-12/biossíntese , Interleucina-12/imunologia , Lactonas/administração & dosagem , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/uso terapêutico , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Germacrano/administração & dosagem , Sesquiterpenos de Germacrano/isolamento & purificação , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de Germacrano/uso terapêutico , Trypanosoma cruzi/isolamento & purificação , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia
13.
PLoS Negl Trop Dis ; 10(11): e0005033, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27820837

RESUMO

BACKGROUND: In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US). However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply. METHODS: In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks). FINDINGS: The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York) have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations. CONCLUSIONS: This study demonstrates a substantial burden of Chagas disease in the US, with state variation that reflects the distribution of at risk Latin American immigrant populations. The study lends important new insight into the distribution of this disease in the US and highlights the need for further research quantifying prevalence and incidence to guide interventions for control of Chagas disease across the US.


Assuntos
Doença de Chagas/epidemiologia , Efeitos Psicossociais da Doença , Adulto , Doadores de Sangue , California/epidemiologia , Doença de Chagas/etnologia , Doença de Chagas/parasitologia , Doença de Chagas/prevenção & controle , Emigrantes e Imigrantes/estatística & dados numéricos , Doenças Endêmicas , Florida/epidemiologia , Humanos , Incidência , América Latina/epidemiologia , Masculino , New York/epidemiologia , Prevalência , Texas/epidemiologia , Texas/etnologia , Trypanosoma cruzi/isolamento & purificação , Estados Unidos/epidemiologia , Estados Unidos/etnologia
14.
PLoS Negl Trop Dis ; 10(11): e0005074, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27832063

RESUMO

BACKGROUND: Chagas disease (Trypanosoma cruzi infection) is the leading cause of non-ischemic dilated cardiomyopathy in Latin America. Texas, particularly the southern region, has compounding factors that could contribute to T. cruzi transmission; however, epidemiologic studies are lacking. The aim of this study was to ascertain the prevalence of T. cruzi in three different mammalian species (coyotes, stray domestic dogs, and humans) and vectors (Triatoma species) to understand the burden of Chagas disease among sylvatic, peridomestic, and domestic cycles. METHODOLOGY/PRINCIPAL FINDINGS: To determine prevalence of infection, we tested sera from coyotes, stray domestic dogs housed in public shelters, and residents participating in related research studies and found 8%, 3.8%, and 0.36% positive for T. cruzi, respectively. PCR was used to determine the prevalence of T. cruzi DNA in vectors collected in peridomestic locations in the region, with 56.5% testing positive for the parasite, further confirming risk of transmission in the region. CONCLUSIONS/SIGNIFICANCE: Our findings contribute to the growing body of evidence for autochthonous Chagas disease transmission in south Texas. Considering this region has a population of 1.3 million, and up to 30% of T. cruzi infected individuals developing severe cardiac disease, it is imperative that we identify high risk groups for surveillance and treatment purposes.


Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Saúde Global , Interações Hospedeiro-Parasita , Insetos Vetores , Trypanosoma cruzi/isolamento & purificação , Animais , Animais Domésticos/parasitologia , Doença de Chagas/complicações , Doença de Chagas/parasitologia , Efeitos Psicossociais da Doença , Coiotes/parasitologia , Cães , Habitação , Humanos , Insetos Vetores/parasitologia , Insetos Vetores/fisiologia , México/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Texas/epidemiologia , Triatoma/parasitologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/fisiologia
15.
ACS Infect Dis ; 2(12): 917-922, 2016 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-27696820

RESUMO

The α-Gal antigen [Galα(1,3)Galß(1,4)GlcNAcα] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of α-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Chagas disease and the assessment of treatment effectiveness. A panel of sera from patients chronically infected with T. cruzi, both untreated and benznidazole-treated, was compared with sera from patients with leishmaniasis and from healthy donors. The nanoparticle-α-Gal construct allowed for perfect discrimination between Chagas patients and the others, avoiding false negative and false positive results obtained with current state-of-the-art reagents. As previously reported with purified α-Gal-containing glycosylphosphatidylinositol-anchored mucins, the current study also showed concentrations of anti-α-Gal IgG to decrease substantially in patients receiving treatment with benznidazole, suggesting that the semiquantitative assessment of serum levels of this highly abundant type of antibody can report on disease status in individual patients.


Assuntos
Doença de Chagas/diagnóstico , Trissacarídeos/análise , Trypanosoma cruzi/isolamento & purificação , Anticorpos Antiprotozoários/análise , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/análise , Antígenos de Protozoários/imunologia , Doença de Chagas/parasitologia , Ensaio de Imunoadsorção Enzimática , Humanos , Trissacarídeos/imunologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/imunologia , Vírus/genética , Vírus/metabolismo
16.
PLoS Negl Trop Dis ; 10(3): e0004528, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27002523

RESUMO

An estimated 2 million inhabitants are infected with Chagas disease in Mexico, with highest prevalence coinciding with highest demographic density in the southern half of the country. After vector-borne transmission, Trypanosoma cruzi is principally transmitted to humans via blood transfusion. Despite initiation of serological screening of blood donations or donors for T. cruzi since 1990 in most Latin American countries, Mexico only finally included mandatory serological screening nationwide in official Norms in 2012. Most recent regulatory changes and segmented blood services in Mexico may affect compliance of mandatory screening guidelines. The objective of this study was to calculate the incremental cost-effectiveness ratio for total compliance of current guidelines from both Mexican primary healthcare and regular salaried worker health service institutions: the Secretary of Health and the Mexican Institute for Social Security. We developed a bi-modular model to analyze compliance using a decision tree for the most common screening algorithms for each health institution, and a Markov transition model for the natural history of illness and care. The incremental cost effectiveness ratio based on life-years gained is US$ 383 for the Secretary of Health, while the cost for an additional life-year gained is US$ 463 for the Social Security Institute. The results of the present study suggest that due to incomplete compliance of Mexico's national legislation during 2013 and 2014, the MoH has failed to confirm 15,162 T. cruzi infections, has not prevented 2,347 avoidable infections, and has lost 333,483 life-years. Although there is a vast difference in T. cruzi prevalence between Bolivia and Mexico, Bolivia established mandatory blood screening for T.cruzi in 1996 and until 2002 detected and discarded 11,489 T. cruzi -infected blood units and prevented 2,879 potential infections with their transfusion blood screening program. In the first two years of Mexico's mandated program, the two primary institutions failed to prevent due to incomplete compliance more potential infections than those gained from the first five years of Bolivia's program. Full regulatory compliance should be clearly understood as mandatory for the sake of blood security, and its monitoring and analysis in Mexico should be part of the health authority's responsibility.


Assuntos
Doença de Chagas/sangue , Doença de Chagas/epidemiologia , Testes Sorológicos/economia , Trypanosoma cruzi/isolamento & purificação , Doadores de Sangue , Doença de Chagas/prevenção & controle , Análise Custo-Benefício , Tomada de Decisões , Custos de Cuidados de Saúde , Humanos , Cadeias de Markov , México/epidemiologia , Programas Nacionais de Saúde , Sensibilidade e Especificidade , Reação Transfusional
17.
Blood Transfus ; 13(4): 540-50, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26513769

RESUMO

In the last decades, increasing international migration and travel from Latin America to Europe have favoured the emergence of tropical diseases outside their "historical" boundaries. Chagas disease, a zoonosis endemic in rural areas of Central and South America represents a clear example of this phenomenon. In the absence of the vector, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products. As most patients with Chagas disease are asymptomatic and unaware of their condition, in case of blood donation they can inadvertently represent a serious threat to the safety of the blood supply in non-endemic areas. Since the first cases of transfusion-transmitted Chagas disease were described in the last years, non-endemic countries began to develop ad hoc strategies to prevent and control the spread of the infection. United States, Spain, United Kingdom and France first recognised the need for Trypanosoma cruzi screening in at-risk blood donors. In this review, we trace an up-to-date perspective on Chagas disease, describing its peculiar features, from epidemiological, pathological, clinical and diagnostic points of view. Moreover, we describe the possible transmission of Chagas disease through blood or blood products and the current strategies for its control, focusing on non-endemic areas.


Assuntos
Doadores de Sangue , Segurança do Sangue , Doença de Chagas/epidemiologia , Reação Transfusional , Adulto , Doadores de Sangue/legislação & jurisprudência , Segurança do Sangue/normas , Doença de Chagas/sangue , Doença de Chagas/congênito , Doença de Chagas/diagnóstico , Doença de Chagas/prevenção & controle , Doença de Chagas/transmissão , Seleção do Doador , Emigração e Imigração , Ensaio de Imunoadsorção Enzimática , Europa (Continente)/epidemiologia , Feminino , Saúde Global , Necessidades e Demandas de Serviços de Saúde , Humanos , Recém-Nascido , América Latina/epidemiologia , América Latina/etnologia , Masculino , Programas de Rastreamento/legislação & jurisprudência , Nifurtimox/uso terapêutico , Nitroimidazóis/uso terapêutico , América do Norte/epidemiologia , Parasitemia/sangue , Parasitemia/diagnóstico , Gravidez , Complicações Infecciosas na Gravidez/parasitologia , Viagem , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/isolamento & purificação
18.
J Parasitol ; 101(5): 520-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26168214

RESUMO

Triatomine bugs are a group of hematophagous arthropods that can serve as biological vectors for Trypanosoma cruzi , the etiological agent of American trypanosomiasis (Chagas disease). Because of differences in the biology and feeding habits among triatomine species, some are more likely than others to be involved in zoonotic and/or human-to-human transmission cycles of T. cruzi . In an attempt to assess the risk for Chagas disease exposure in south-central Texas, human habitations across Texas Health Service Region 8 (HSR 8) and surrounding counties were surveyed for triatomines to characterize the geographic distribution, species-specific biology, and T. cruzi -infection prevalence better. Between May 2010 and August 2013, a total of 545 triatomines representing all 5 known indigenous species (Triatoma gerstaeckeri, Triatoma indictiva, Triatoma lecticularia, Triatoma sanguisuga, and Triatoma protracta woodi) were collected from 59 sites across the region. Triatoma gerstaeckeri was the species most commonly found in domestic and peridomestic ecotopes across Texas HSR 8, representing over 80% of the triatomines collected. Adult T. gerstaeckeri exhibited a seasonal dispersal pattern that began in late April, peaked in mid-May, and then continued into August. On homes with available crevices in the exterior walls, adult T. gerstaeckeri were observed emerging from or entering these protective microhabitats, suggesting possible opportunistic colonization of some exterior walls compartments. Laboratory testing of triatomine hindgut contents for T. cruzi by PCR demonstrated the adult T. gerstaeckeri-infection prevalence across Texas HSR 8 to be 64%. Monitoring peridomestic adult T. gerstaeckeri over the seasonal dispersal peak demonstrated statistically significant increases in both their T. cruzi -infection prevalence (P < 0.01) and tendency to invade human dwellings (P < 0.01) in the later aspect of the emergence peak. In addition to the adult insects, variably sized and staged nymphs were recovered from the inside of 6 separate homes across Texas HSR 8. The results of this study show that T. gerstaeckeri is a widespread and common triatomine species across Texas HSR 8 and documented it to have some notable synanthropic tendencies. The high prevalence of T. cruzi infection in native triatomines, and the high frequency with which T. gerstaeckeri is recovered from human habitations, suggests that there is a risk for human exposure to T. cruzi in Texas HSR 8. Because of this, Chagas disease should be considered on the list of differential diagnoses for cases of cardiac arrhythmia, dilated cardiomyopathy, or heart failure in south-central Texas.


Assuntos
Doença de Chagas/transmissão , Insetos Vetores/anatomia & histologia , Triatoma/anatomia & histologia , Trypanosoma cruzi/isolamento & purificação , Animais , Doença de Chagas/epidemiologia , Feminino , Humanos , Mordeduras e Picadas de Insetos/epidemiologia , Insetos Vetores/classificação , Insetos Vetores/parasitologia , Masculino , Especificidade da Espécie , Texas/epidemiologia , Triatoma/classificação , Triatoma/parasitologia , Trypanosoma cruzi/fisiologia
19.
Trans R Soc Trop Med Hyg ; 109(2): 143-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25604765

RESUMO

BACKGROUND: Non-domiciliated (intrusive) triatomine vectors remain a challenge for the sustainability of Chagas disease vector control as these triatomines are able to transiently (re-)infest houses. One of the best-characterized examples is Triatoma dimidiata from the Yucatan peninsula, Mexico, where adult insects seasonally infest houses between March and July. METHODS: We focused our study on three rural villages in the state of Yucatan, Mexico, in which we performed a situation analysis as a first step before the implementation of an ecohealth (ecosystem approach to health) vector control intervention. RESULTS: The identification of the key determinants affecting the transient invasion of human dwellings by T. dimidiata was performed by exploring associations between bug presence and qualitative and quantitative variables describing the ecological, biological and social context of the communities. We then used a participatory action research approach for implementation and evaluation of a control strategy based on window insect screens to reduce house infestation by T. dimidiata. CONCLUSIONS: This ecohealth approach may represent a valuable alternative to vertically-organized insecticide spraying. Further evaluation may confirm that it is sustainable and provides effective control (in the sense of limiting infestation of human dwellings and vector/human contacts) of intrusive triatomines in the region.


Assuntos
Doença de Chagas/prevenção & controle , Habitação/normas , Controle de Insetos/organização & administração , Triatoma/crescimento & desenvolvimento , Trypanosoma cruzi/patogenicidade , Animais , Doença de Chagas/transmissão , Reservatórios de Doenças , Ecossistema , Interações Hospedeiro-Parasita , Humanos , Insetos Vetores , México/epidemiologia , Inovação Organizacional , Vigilância da População , Características de Residência , População Rural , Estações do Ano , Triatoma/parasitologia , Trypanosoma cruzi/isolamento & purificação
20.
Trans R Soc Trop Med Hyg ; 109(2): 150-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25604766

RESUMO

BACKGROUND: Triatoma infestans is the main vector of Chagas disease in the southern cone countries. Present control strategies based on indoor and outdoor residual insecticide spraying are not sufficient to control disease transmission, particularly in Bolivia. Techniques based on the management of the human environment may be good alternatives or supplements. METHODS: Social and entomological surveys were carried out in four villages of Bolivia situated in the dry inter-Andean Valleys and the Chaco region. Risk factors for house infestation by T. infestans were identified, and an eco-health intervention based on education and community participation was carried out to reduce the risks of house infestation. It consisted of implementing simple and low cost vector control techniques such as coating of mud walls, cleaning activities and removal of poultry that enter rooms to lay eggs. RESULTS: The eco-health intervention significantly reduced the number of infested bedrooms, the mean abundance of T. infestans in bedrooms and beds, especially in the Chaco region. Mud wall coating was well accepted and could be proposed as a supplementary tool to the National Program of Chagas Disease Control to enhance the effects of insecticide sprayings. CONCLUSIONS: Even if cleaning activities were still neglected, community participation proved to be effective in reducing house infestation.


Assuntos
Doença de Chagas/prevenção & controle , Participação da Comunidade/estatística & dados numéricos , Habitação , Controle de Insetos/organização & administração , Triatoma/parasitologia , Trypanosoma cruzi/patogenicidade , Animais , Bolívia/epidemiologia , Doença de Chagas/transmissão , Serviços de Saúde Comunitária/organização & administração , Grupos Focais , Educação em Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Insetos Vetores , Inseticidas , População Rural , Estações do Ano , Inquéritos e Questionários , Trypanosoma cruzi/isolamento & purificação
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