Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis

Detalhes bibliográficos
Autor(a) principal: Souza, Fernanda Mattos de
Data de Publicação: 2022
Outros Autores: fernandamattosdesouza@yahoo.com.br
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/19239
Resumo: This thesis aimed to identify screening strategies for tuberculosis infection (TBI) in healthcare workers (HCW) that enable the most efficient use of available resources. Investigation of TBI in HCWs is recommended in Brazil as part of the worker's pre-employment and periodic (annual) health visits. HCWs with a first tuberculin skin test (TST) induration < 10 mm are invited to repeat the test in one to three weeks to assess the booster effect (induration size increment of 10 mm). Those with a persistent TST < 10 mm will undergo a one-step TST every 12 months. TPT is recommended when conversion (10 mm increment over latest induration size) occurs. We developed, in the first manuscript, a predictive model to identify HCWs best targeted for TBI screening. We carried out a secondary analysis of previously published results of 708 HCWs working in primary care services in five Brazilian State capitals who underwent two TBI tests: tuberculin skin test and Quantiferon®-TB Gold in-tube. We used a classification and regression tree (CART) model to predict HCWs with negative results for both tests. The performance of the model was evaluated using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), cross-validated using the same dataset. Among the 708 HCWs, 247 (34.9%) had negative results for both tests. CART allowed us to identify that physicians or a community health agents were twice more likely to be uninfected (probability = 0.60) than registered or aid nurse (probability = 0.28) when working less than 5.5 years in the primary care setting. In cross validation, the predictive accuracy was 68% [95% confidence interval (95%CI): 65 – 71], AUC was 62% (95%CI 58 – 66), specificity was 78% (95%CI 74 – 81), and sensitivity was 44% (95%CI 38 – 50). Despite the low predictive power of this model, CART allowed to identify subgroups with higher probability of having both tests negative. In the second manuscript, we analyzed the cost-effectiveness of two TB antigen-based skin tests (TBST) using the recombinant ESAT-6 and CFP-10 immunogens (Diaskintest® and C-TST®) and of QFT-Plus® for TBI diagnosis compared with the current standard of care, TST, among HCWs in Brazil. A state-transition Markov model was created, simulating a cohort of 100,000 HCWs (five annual cycles) for TBI treatment scenarios with 3 months of weekly doses of rifapentine (900 mg) and isoniazid (900 mg) (3HP). We adopted the Brazilian public health system perspective. Effects [tuberculosis disease (TBD) averted) and costs for screening and treating TBI were discounted at 5%. Incremental cost-effectiveness per TBD averted was calculated. Hypothetical cohort of 100,000 HCWs of both sexes with a negative result of TST in the previous year. Diaskintest®, C-TST® and QFT-Plus® tests have higher specificity (0.98, 0.98 and 0.97, respectively). Costs with QFT-Plus® were higher due to equipment, human labor and cost of the kit by test. Diaskintest® was the most cost-effective test (US$ 7,042, US$ 5,781, and US$18,892 per case of TBD averted for the 3HP, 6H, and 9H treatment regimens, respectively), including sensitivity analyses. In the Brazilian scenario, Diaskintest® is the most cost-effective test for sequential testing of HCWs.
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spelling Trajman, AneteSteffen, Ricardo EwbankPinto, Márcia TeixeiraMaciel, Ethel Leonor NoiaBraga, José UeleresDal Poz, Mario Robertohttp://lattes.cnpq.br/5558850052125575Souza, Fernanda Mattos defernandamattosdesouza@yahoo.com.br2023-03-29T14:09:00Z2024-08-252022-08-26SOUZA, Fernanda Mattos de. Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis. 2022. 201 f. Tese (Doutorado em Saúde Coletiva) - Instituto de Medicina Social Hesio Cordeiro, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2022.http://www.bdtd.uerj.br/handle/1/19239This thesis aimed to identify screening strategies for tuberculosis infection (TBI) in healthcare workers (HCW) that enable the most efficient use of available resources. Investigation of TBI in HCWs is recommended in Brazil as part of the worker's pre-employment and periodic (annual) health visits. HCWs with a first tuberculin skin test (TST) induration < 10 mm are invited to repeat the test in one to three weeks to assess the booster effect (induration size increment of 10 mm). Those with a persistent TST < 10 mm will undergo a one-step TST every 12 months. TPT is recommended when conversion (10 mm increment over latest induration size) occurs. We developed, in the first manuscript, a predictive model to identify HCWs best targeted for TBI screening. We carried out a secondary analysis of previously published results of 708 HCWs working in primary care services in five Brazilian State capitals who underwent two TBI tests: tuberculin skin test and Quantiferon®-TB Gold in-tube. We used a classification and regression tree (CART) model to predict HCWs with negative results for both tests. The performance of the model was evaluated using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), cross-validated using the same dataset. Among the 708 HCWs, 247 (34.9%) had negative results for both tests. CART allowed us to identify that physicians or a community health agents were twice more likely to be uninfected (probability = 0.60) than registered or aid nurse (probability = 0.28) when working less than 5.5 years in the primary care setting. In cross validation, the predictive accuracy was 68% [95% confidence interval (95%CI): 65 – 71], AUC was 62% (95%CI 58 – 66), specificity was 78% (95%CI 74 – 81), and sensitivity was 44% (95%CI 38 – 50). Despite the low predictive power of this model, CART allowed to identify subgroups with higher probability of having both tests negative. In the second manuscript, we analyzed the cost-effectiveness of two TB antigen-based skin tests (TBST) using the recombinant ESAT-6 and CFP-10 immunogens (Diaskintest® and C-TST®) and of QFT-Plus® for TBI diagnosis compared with the current standard of care, TST, among HCWs in Brazil. A state-transition Markov model was created, simulating a cohort of 100,000 HCWs (five annual cycles) for TBI treatment scenarios with 3 months of weekly doses of rifapentine (900 mg) and isoniazid (900 mg) (3HP). We adopted the Brazilian public health system perspective. Effects [tuberculosis disease (TBD) averted) and costs for screening and treating TBI were discounted at 5%. Incremental cost-effectiveness per TBD averted was calculated. Hypothetical cohort of 100,000 HCWs of both sexes with a negative result of TST in the previous year. Diaskintest®, C-TST® and QFT-Plus® tests have higher specificity (0.98, 0.98 and 0.97, respectively). Costs with QFT-Plus® were higher due to equipment, human labor and cost of the kit by test. Diaskintest® was the most cost-effective test (US$ 7,042, US$ 5,781, and US$18,892 per case of TBD averted for the 3HP, 6H, and 9H treatment regimens, respectively), including sensitivity analyses. In the Brazilian scenario, Diaskintest® is the most cost-effective test for sequential testing of HCWs.Esta tese objetivou identificar estratégias de triagem para infecção latente por Mycobacterium tuberculosis (Mtb) – ILTB em profissionais de saúde que viabilizem o uso mais eficiente dos recursos disponíveis. No Brasil, recomenda-se que os profissionais de saúde, um dos grupos de risco para a ILTB, realizem triagem periódica para detecção da infecção e aqueles que apresentarem conversão aos testes de diagnóstico, indica-se o tratamento preventivo da tuberculose (TB) – TPT uma vez que pessoas com conversão recente apresentam elevada chance de progressão para a doença. Desenvolvemos, no primeiro artigo, um modelo preditivo para identificar profissionais de saúde com maior probabilidade de resultado negativo para dois testes de diagnóstico da ILTB a partir de uma análise secundária de dados publicados anteriormente de 708 profissionais de saúde da atenção primária, de cinco capitais brasileiras, submetidos à prova tuberculínica (PT) e ao Quantiferon®-TB Gold in-tube (QFT-IT®). Construímos um modelo preditivo utilizando árvore de classificação e regressão (CART, classification and regression tree). A avaliação do desempenho foi realizada por meio da análise receiver operating characteristics (ROC) e area under the curve (AUC). Utilizou-se o mesmo banco de dados para validação cruzada do modelo. Entre os 708 profissionais de saúde, 247 (34,9%) apresentaram resultado negativo para os testes. A CART identificou que os médicos e agentes comunitários de saúde apresentaram chances duas vezes maior de testes negativos (probabilidade = 0,60) do que os enfermeiros e técnicos/auxiliares de enfermagem (probabilidade = 0,28) naqueles com menos de 5,5 anos de atuação na atenção primária. Na validação cruzada, a acurácia do modelo preditivo foi de 68% [intervalo de confiança de 95% (IC95%) 65 – 71) ], AUC de 62% (IC95% 58 – 66), especificidade de 78% (IC95% 74 – 81) e sensibilidade de 44% (IC95% 38 – 50). Apesar do baixo poder preditivo do modelo, a CART permitiu identificar subgrupos com maior probabilidade de terem ambos os testes negativos. No segundo artigo, analisou-se a razão de custo-efetividade de dois testes de sensibilidade cutânea baseados em antígenos específicos do Mtb -Diaskintest® e C-TST® - e a do QFT-Plus® para o diagnóstico da ILTB comparadas com a estratégia diagnóstica atual (PT) entre profissionais de saúde. Desenvolveu-se um modelo analítico de decisão, representado por coorte hipotética de 100.000 profissionais de saúde, de ambos os sexos, com resultado negativo para a PT no ano anterior, horizonte temporal de cinco anos, na perspectiva do Sistema Único de Saúde. Avaliaram-se três regimes de tratamento para a ILTB: três meses de doses semanais de rifapentina (900 mg) e isoniazida (900 mg) (3HP), seis e nove meses de doses diárias de isoniazida (300 mg) (6H e 9H, respectivamente). Aplicou-se taxa de desconto de 5% na efetividade, medida em casos de TB ativa evitados, e nos custos das estratégias de triagem e de tratamento avaliados, estimados em dólares americanos (US$) com taxa média anual de 2021 de acordo com o Banco Central (US$ 1 = 5,39 reais). Foram realizadas análises de sensibilidade determinística univariada e probabilística. Os testes Diaskintest®, C-TST® e QFT-Plus® apresentam maior especificidade (0,98, 0,98 e 0,97, respectivamente). Os custos com QFT-Plus® foram maiores devido aos equipamentos, mão de obra e ao custo do kit. O Diaskintest® foi o teste mais econômico (US$ 7.042, US$ 5.781 e US$ 18.892 por caso de TB ativa evitado para os regimes de tratamento com 3HP, 6H e 9H, respectivamente), inclusive nas análises de sensibilidade. No cenário nacional, o Diaskintest® foi o teste de melhor custo-efetividade para avaliação anual dos profissionais de saúde.Submitted by Marcia CB/C (marciagraziadio@yahoo.com.br) on 2023-03-29T14:09:00Z No. of bitstreams: 2 Tese - Fernanda Mattos de Souza - 2022 - Completa.pdf: 3486561 bytes, checksum: b864f2d167021f8d473e6819ccc49a96 (MD5) Tese - Fernanda Mattos de Souza - 2022 - Parcial.pdf: 1884556 bytes, checksum: 93ce9a0de2ea9bd92cb2ab3ea2c21c71 (MD5)Made available in DSpace on 2023-03-29T14:09:00Z (GMT). No. of bitstreams: 2 Tese - Fernanda Mattos de Souza - 2022 - Completa.pdf: 3486561 bytes, checksum: b864f2d167021f8d473e6819ccc49a96 (MD5) Tese - Fernanda Mattos de Souza - 2022 - Parcial.pdf: 1884556 bytes, checksum: 93ce9a0de2ea9bd92cb2ab3ea2c21c71 (MD5) Previous issue date: 2022-08-26application/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Saúde ColetivaUERJBrasilCentro Biomédico::Instituto de Medicina Social Hesio CordeiroLatent tuberculosisHealthcare workersDecision treesHealth technologyEconomic evaluationsTuberculose latenteTeste de diagnósticoProfissionais de saúdeÁrvores de decisõesAvaliação de tecnologias em saúdeAnálise de custo-efetividadeCIENCIAS DA SAUDE::SAUDE COLETIVANovas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosisNew tools for the diagnostics of latent Mycobacterium tuberculosis infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/embargoedAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTese - Fernanda Mattos de Souza - 2022 - Completa.pdfTese - Fernanda Mattos de Souza - 2022 - Completa.pdfapplication/pdf3486561http://www.bdtd.uerj.br/bitstream/1/19239/2/Tese+-+Fernanda+Mattos+de+Souza+-+2022+-+Completa.pdfb864f2d167021f8d473e6819ccc49a96MD52Tese - Fernanda Mattos de Souza - 2022 - Parcial.pdfTese - Fernanda Mattos de Souza - 2022 - Parcial.pdfapplication/pdf1884556http://www.bdtd.uerj.br/bitstream/1/19239/3/Tese+-+Fernanda+Mattos+de+Souza+-+2022+-+Parcial.pdf93ce9a0de2ea9bd92cb2ab3ea2c21c71MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/19239/1/license.txte5502652da718045d7fcd832b79fca29MD511/192392024-02-26 20:20:40.354oai:www.bdtd.uerj.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T23:20:40Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
dc.title.alternative.eng.fl_str_mv New tools for the diagnostics of latent Mycobacterium tuberculosis infection
title Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
spellingShingle Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
Souza, Fernanda Mattos de
Latent tuberculosis
Healthcare workers
Decision trees
Health technology
Economic evaluations
Tuberculose latente
Teste de diagnóstico
Profissionais de saúde
Árvores de decisões
Avaliação de tecnologias em saúde
Análise de custo-efetividade
CIENCIAS DA SAUDE::SAUDE COLETIVA
title_short Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
title_full Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
title_fullStr Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
title_full_unstemmed Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
title_sort Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis
author Souza, Fernanda Mattos de
author_facet Souza, Fernanda Mattos de
fernandamattosdesouza@yahoo.com.br
author_role author
author2 fernandamattosdesouza@yahoo.com.br
author2_role author
dc.contributor.advisor1.fl_str_mv Trajman, Anete
dc.contributor.advisor-co1.fl_str_mv Steffen, Ricardo Ewbank
dc.contributor.referee1.fl_str_mv Pinto, Márcia Teixeira
dc.contributor.referee2.fl_str_mv Maciel, Ethel Leonor Noia
dc.contributor.referee3.fl_str_mv Braga, José Ueleres
dc.contributor.referee4.fl_str_mv Dal Poz, Mario Roberto
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5558850052125575
dc.contributor.author.fl_str_mv Souza, Fernanda Mattos de
fernandamattosdesouza@yahoo.com.br
contributor_str_mv Trajman, Anete
Steffen, Ricardo Ewbank
Pinto, Márcia Teixeira
Maciel, Ethel Leonor Noia
Braga, José Ueleres
Dal Poz, Mario Roberto
dc.subject.eng.fl_str_mv Latent tuberculosis
Healthcare workers
Decision trees
Health technology
Economic evaluations
topic Latent tuberculosis
Healthcare workers
Decision trees
Health technology
Economic evaluations
Tuberculose latente
Teste de diagnóstico
Profissionais de saúde
Árvores de decisões
Avaliação de tecnologias em saúde
Análise de custo-efetividade
CIENCIAS DA SAUDE::SAUDE COLETIVA
dc.subject.por.fl_str_mv Tuberculose latente
Teste de diagnóstico
Profissionais de saúde
Árvores de decisões
Avaliação de tecnologias em saúde
Análise de custo-efetividade
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::SAUDE COLETIVA
description This thesis aimed to identify screening strategies for tuberculosis infection (TBI) in healthcare workers (HCW) that enable the most efficient use of available resources. Investigation of TBI in HCWs is recommended in Brazil as part of the worker's pre-employment and periodic (annual) health visits. HCWs with a first tuberculin skin test (TST) induration < 10 mm are invited to repeat the test in one to three weeks to assess the booster effect (induration size increment of 10 mm). Those with a persistent TST < 10 mm will undergo a one-step TST every 12 months. TPT is recommended when conversion (10 mm increment over latest induration size) occurs. We developed, in the first manuscript, a predictive model to identify HCWs best targeted for TBI screening. We carried out a secondary analysis of previously published results of 708 HCWs working in primary care services in five Brazilian State capitals who underwent two TBI tests: tuberculin skin test and Quantiferon®-TB Gold in-tube. We used a classification and regression tree (CART) model to predict HCWs with negative results for both tests. The performance of the model was evaluated using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), cross-validated using the same dataset. Among the 708 HCWs, 247 (34.9%) had negative results for both tests. CART allowed us to identify that physicians or a community health agents were twice more likely to be uninfected (probability = 0.60) than registered or aid nurse (probability = 0.28) when working less than 5.5 years in the primary care setting. In cross validation, the predictive accuracy was 68% [95% confidence interval (95%CI): 65 – 71], AUC was 62% (95%CI 58 – 66), specificity was 78% (95%CI 74 – 81), and sensitivity was 44% (95%CI 38 – 50). Despite the low predictive power of this model, CART allowed to identify subgroups with higher probability of having both tests negative. In the second manuscript, we analyzed the cost-effectiveness of two TB antigen-based skin tests (TBST) using the recombinant ESAT-6 and CFP-10 immunogens (Diaskintest® and C-TST®) and of QFT-Plus® for TBI diagnosis compared with the current standard of care, TST, among HCWs in Brazil. A state-transition Markov model was created, simulating a cohort of 100,000 HCWs (five annual cycles) for TBI treatment scenarios with 3 months of weekly doses of rifapentine (900 mg) and isoniazid (900 mg) (3HP). We adopted the Brazilian public health system perspective. Effects [tuberculosis disease (TBD) averted) and costs for screening and treating TBI were discounted at 5%. Incremental cost-effectiveness per TBD averted was calculated. Hypothetical cohort of 100,000 HCWs of both sexes with a negative result of TST in the previous year. Diaskintest®, C-TST® and QFT-Plus® tests have higher specificity (0.98, 0.98 and 0.97, respectively). Costs with QFT-Plus® were higher due to equipment, human labor and cost of the kit by test. Diaskintest® was the most cost-effective test (US$ 7,042, US$ 5,781, and US$18,892 per case of TBD averted for the 3HP, 6H, and 9H treatment regimens, respectively), including sensitivity analyses. In the Brazilian scenario, Diaskintest® is the most cost-effective test for sequential testing of HCWs.
publishDate 2022
dc.date.issued.fl_str_mv 2022-08-26
dc.date.accessioned.fl_str_mv 2023-03-29T14:09:00Z
dc.date.available.fl_str_mv 2024-08-25
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv SOUZA, Fernanda Mattos de. Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis. 2022. 201 f. Tese (Doutorado em Saúde Coletiva) - Instituto de Medicina Social Hesio Cordeiro, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2022.
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identifier_str_mv SOUZA, Fernanda Mattos de. Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis. 2022. 201 f. Tese (Doutorado em Saúde Coletiva) - Instituto de Medicina Social Hesio Cordeiro, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2022.
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