RESUMO
Trypanosoma cruzi, the protozoan agent of Chagas' disease, displays a complex population structure made up of multiple strains showing a diverse ecoepidemiological distribution. Parasite genetic variability may be associated with disease outcome, hence stressing the need to develop methods for T. cruzi typing in vivo. Serological typing methods that exploit the presence of host antibodies raised against polymorphic parasite antigens emerge as an appealing approach to address this issue. These techniques are robust, simple, cost-effective, and are not curtailed by methodological/biological limitations intrinsic to available genotyping methods. Here, we critically assess the progress towards T. cruzi serotyping and discuss the opportunity provided by high-throughput immunomics to improve this field.
Assuntos
Parasitologia/métodos , Testes Sorológicos/normas , Trypanosoma cruzi/classificação , Animais , Doença de Chagas/parasitologia , Humanos , Testes Sorológicos/economia , Testes Sorológicos/tendências , Especificidade da Espécie , Trypanosoma cruzi/imunologiaRESUMO
Human visceral leishmaniasis (VL) is a severe and potentially fatal parasitic disease if not correctly diagnosed and treated. Brazil is one of the three countries most endemic for VL and, like most countries affected by this disease, has a large budget constraint for the incorporation of new health technologies. Although different diagnostic tests for VL are currently available in the country, economic studies evaluating diagnostic kits are scarce. The objective of this study was to conduct a cost-effectiveness analysis of the nine available diagnostic tests for human VL in HIV-infected and uninfected patients in Brazil. The perspective of analysis was the Brazilian public health system, and the outcome of interest was "cases diagnosed correctly". The costs of the tests were estimated using the microcosting technique, and comparisons were performed with decision trees. Sensitivity analyses were explored applying variations in cost and effectiveness values. For VL diagnosis among HIV-uninfected patients, using blood samples for the rapid tests (RDTs), the noncommercial direct agglutination test (DAT-LPC) and IT-LEISH were cost-effective tests compared with the baseline OnSite test, but they presented different incremental cost-effectiveness ratios (ICER) of US$7.04 and US$ 205.40, respectively. Among HIV-infected patients, DAT-LPC was the most cost-effective diagnostic test. Comparisons among the tests with the same methodology, based on the low ICER values, revealed that IT-LEISH was the most cost-effective test among the RDTs and the Ridascreen Leishmania Ab among the ELISA tests. These results confirm that cost-effectiveness analyses can provide useful information to support the incorporation of new health technologies within a known scenario and willingness to pay threshold. It was observed that tests based on the same methodologies presented different cost-effectiveness ratios for the same group of patients and that different tests should be recommended for different patient groups. DAT-LPC was an important cost-effective strategy for all patients, requiring minimum laboratorial infrastructure, and IT-LEISH was the cost-effective test for VL screening in HIV-uninfected patients. IT-LEISH and DAT-LPC have complementary profiles and should both be provided by the Brazilian health system.
Assuntos
Análise Custo-Benefício , Custos de Cuidados de Saúde , Leishmaniose Visceral/diagnóstico , Testes Sorológicos/economia , Testes Sorológicos/métodos , Brasil , Humanos , Leishmaniose Visceral/economia , Kit de Reagentes para Diagnóstico , Sensibilidade e EspecificidadeRESUMO
Toxocariasis is a neglected zoonosis that affects children and adults. Recombinant proteins have been widely investigated for diagnosis, achieving high sensitivity and specificity in an overall population; however, little is known about age as a factor in its application. This study aims to investigate the diagnostic potential of Toxocara canis TES-30 and TES-120 recombinant proteins in humans, differentiating between its performance in children and adults. Serum samples collected from children and adults seropositive to Toxocara spp. were tested with indirect ELISA using T. canis TES-30 and TES-120 recombinant proteins produced in Escherichia coli. While rTES-30 sensitivity was not affected by age (81.8% in children and 87% in adults), rTES-120 sensitivity severely decreased in children to only 63.6%, down from 95.7% in adults. Furthermore, the sensitivity of rTES-30 increased to 97.8% after Western blotting confirmation. High specificity (>94%) against other geohelminths was reported for both recombinant proteins. Our study favors the use of rTES-30 with total IgG as the primary antibody in an indirect ELISA assay as a tool for epidemiological human studies.
Assuntos
Proteínas Recombinantes/metabolismo , Testes Sorológicos/métodos , Toxocara , Adulto , Animais , Criança , Pré-Escolar , Custos e Análise de Custo , Humanos , Lactente , Prognóstico , Sensibilidade e Especificidade , Testes Sorológicos/economia , Fatores de TempoAssuntos
Infecções por HIV/diagnóstico , Programas de Rastreamento , Autorrelato , Adolescente , Adulto , Custos e Análise de Custo , Feminino , HIV/patogenicidade , Humanos , Quênia , Masculino , Testes Sorológicos/economia , Testes Sorológicos/métodos , Parceiros Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto JovemRESUMO
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 JovemRESUMO
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 TransfusionalRESUMO
Patients with hepatitis C virus (HCV) infection are detected by testing for the presence of antibodies to HCV (Anti-HCV). A positive Anti-HCV test represents a true positive result only in a variable proportion of subjects (35 to 95%). The qualitative interpretation as positive or negative Anti-HCV report is associated with a general lack of understanding regarding the interpretation of results, when more specific testing should be performed, and which tests should be considered for this purpose. Therefore, a substantial variation in supplemental testing practices exists among laboratories and physicians. This guideline was developed on the basis of the best available evidence to classify positive antibody in two (low and high) or three levels (very low, low and high) according to the signal to cutoff (S/CO) ratio: the very low level of the Anti-HCV identifies false-positive results and further diagnostic testing is not necessary. The low antibody level is frequently related with false-positive results and testing with Immunoblot is recommended; only Immunoblot-positive subjects require HCV RNA testing because of a low possibility of being viremic. The high Anti-HCV level is an accurate serological marker for predicting viremia and denotes the need of routine HCV RNA testing in order to efficiently confirm hepatitis C. Cost-effectiveness analysis, based on the Anti-HCV level, recommends the use of the two or three-levels to choose the confirmatory test of positive antibody. This approach can be implemented without increasing test costs because the S/CO ratio is automatically generated in most laboratory analyzers and would provide health care professionals with useful information for counseling and evaluating patients, to eliminate unwarranted notifications in cases of false antibody reactivity, and correctly identifying those Anti-HCV-positive patients who are infected and need antiviral treatment. The written report should include the antibody level (S/CO ratio), the type of the immunoassay applied and interpretation guideline. Anti-HCV testing is performed in multiple settings including blood banks or health department facilities; adoption of this Guideline for interpretation and report of the antibody to hepatitis C virus by laboratories and its implementation by clinicians will improve the accuracy for interpreting antibody result to determine the next step on hepatitis C diagnosis.
Assuntos
Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , Testes Sorológicos/métodos , Algoritmos , Doadores de Sangue , Segurança do Sangue , Análise Custo-Benefício , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Reações Falso-Negativas , Reações Falso-Positivas , Controle de Formulários e Registros , Hepacivirus/genética , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite C/sangue , Hepatite C/economia , Hepatite C/epidemiologia , Hepatite C/transmissão , Humanos , Imunoensaio/métodos , Immunoblotting/métodos , México , Valor Preditivo dos Testes , RNA Viral/sangue , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Testes Sorológicos/economiaRESUMO
UNLABELLED: In this prospective study we evaluated the performance characteristics of a specific and sensitive antigen preparation (AgA) used in an enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Trypanosoma cruzi antibodies in serum samples, for Chagas' disease diagnosis. The antigen production was achieved by combination of nutritional stress and autoclaving the parasites. Specificity and sensitivity were evaluated in two separate tests, using 152 sera from healthy individuals and 175 sera from Chagas' patients (70 by xenodiagnosis). Cross-reactivity was tested using 289 sera from patients who had a parasitological diagnosis of a disease known to induce antigenic responses towards T. cruzi. All of these sera were tested with our AgA-ELISA and with 3 commercial diagnosis kits. To evaluate the agreement of results between our AgA-ELISA and a "gold standard" test for Chagas, we tested 566 sera from an endemic area. RESULTS: sensitivity and specificity were 100%; cross-reactivity was the lowest compared with commercial kits. Overall agreement with the gold standard test was excellent (kappa = 0.92). AgA-ELISA exhibits levels of sensitivity, specificity and cross-reactivity comparable or superior to those shown, obtained with the commercial kits used in our country, while being at least 10 times less expensive. This balance between diagnostic accuracy and cost makes AgA-ELISA useful for blood bank screening in poor regions of the world suffering from Chagas' disease. Further validations of this antigenic formulation in other countries are necessary.
Assuntos
Antígenos de Protozoários/sangue , Doença de Chagas/sangue , Doença de Chagas/diagnóstico , Ensaio de Imunoadsorção Enzimática , Trypanosoma cruzi/imunologia , Custos e Análise de Custo , Humanos , Testes Sorológicos/economiaRESUMO
Para avaliar reduçäo de custo da pesquisa de anticorpos contra hepatite C, por ELISA, em pool de cinco soros, realizou-se o teste em grupos de baixo e alto risco. Dois terços dos conjuntos de alto risco tiveram que ser repetidos. A reduçäo do gasto de reagente foi de 80 por cento na populaçäo de baixo risco e de 13 por cento na amostra de alto risco. Estes dados sugerem que a pesquisa do anti-VHC em pool reduz o custo do procedimento em populaçöes de baixo risco