Incrementando o impacto do diagnóstico e do tratamento da infecção latente tuberculosa na saúde pública: um estudo de efetividade, sustentabilidade, viabilidade e custo-efetividade / A public health approach to increase treatment of latent tuberculosis infection: a study of effectiveness, sustainability, feasibility and cost-effectiveness

O tratamento da infecção latente da tuberculose (ILTB) é crucial para eliminar a doença. Esta tese, apresentada em dois artigos, avalia a efetividade, a sustentabilidade, a viabilidade, a razão de custo-efetividade e o impacto orçamentário de um programa de investigação para detecção e tratamento da ILTB em contatos intradomiciliares de pacientes com tuberculose no Brasil. No primeiro artigo, dois ensaios controlados consecutivos foram conduzidos. Avaliamos a efetividade, a sustentabilidade, e a viabilidade de uma intervenção em saúde pública que teve o objetivo de aumentar a proporção de início do tratamento para ILTB entre os contatos intradomiciliares de pacientes com tuberculose pulmonar ativa. No primeiro ensaio clínico controlado, 12 clínicas foram submetidas a uma avaliação padronizada, incluindo questionários administrados a pacientes com tuberculose, seus contatos intradomiciliares e profissionais de saúde, e uma análise da cascata do cuidado da ILTB. Seis clínicas foram então randomizadas para receber atividades para fortalecer o manejo da ILTB, incluindo treinamento em serviço, organização do processo de trabalho e soluções adicionais específicas de cada clínica de acordo com resultados da avaliação padronizada. No segundo ensaio, uma avaliação semelhante, mas simplificada, foi realizada em duas clínicas, que então receberam treinamento intensivo inicial e treinamento em serviço fornecido por um médico. No segundo artigo, avaliamos a razão de custo-efetividade e o impacto orçamentário ao expandir um programa fortalecido de investigação e tratamento da ILTB entre contatos intradomiciliares no Brasil. Duas estratégias otimizadas sobre o manejo dos contatos intradomiciliares foram comparadas com a situação atual (status quo) no Brasil: 1) detecção de tuberculose ativa apenas e 2) detecção de tuberculose ativa e investigação e tratamento de ILTB. Nos dois ensaios controlados, na fase de avaliação, foram observadas lacunas de conhecimento entre todos os grupos de entrevistados e, embora muitos contatos tenham sido identificados, poucos iniciaram o tratamento de ILTB. Após a implementação das soluções, o número de contatos que iniciaram o tratamento da ILTB por 100 pacientes com tuberculose aumentou em 10 [intervalo de 95% de confiança (IC): -11, 30] no primeiro estudo, em comparação com 44 (IC 95%: 26, 61), no segundo ensaio controlado. Em nossas avaliações econômicas, na estratégia otimizada de investigação e tratamento da ILTB os custos para ter um contato intradomiciliar completando o tratamento da ILTB seriam a metade daqueles para encontrar um paciente com TB ativa (158,6 vs. 299,7 dólares norte-americanos). Resultariam ainda em um importante impacto na endemia, 4.001 casos de TB seriam evitados e custariam 12% do orçamento nacional para TB. Uma abordagem de saúde pública com avaliação padronizada, seguida por treinamento inicial e treinamento em serviço intensivo mostrou-se promissora para expandir o tratamento da ILTB no Brasil.

This thesis, presented in two articles, evaluates the effectiveness, sustainability, feasibility, cost-effectiveness and budgetary impact of a program that investigates and treats latent tuberculosis infection (LTBI) among household contacts (HHC) of patients with active tuberculosis in Brazil. In the first article, we presented the results of two consecutive control trials, where we evaluated the effectiveness, sustainability and feasibility a public health intervention that aimed to increase the proportion of initiation of treatment for ILTB among HHC of patients with active tuberculosis. In the first trial, twelve clinics underwent a standardized evaluation, including questionnaires administered to tuberculosis-patients, contacts and healthcare workers and clinical data on the cascade-of-care for contacts. Six clinics were then randomized to receive LTBI strengthening activities, including monthly in-service training work process organization, and implementation of specific local solutions. In the second trial, a similar but streamlined evaluation was conducted in two clinics, who then received initial and subsequent intensive in-service training provided by a physician. In the second article, we evaluated the cost-effectiveness and budget impact of scaling-up an enhanced tuberculosis HHC program in Brazil. Two enhanced HHC management strategies were compared to the current HHC management situation in Brazil (status quo). HHC cascades-of-care were conceptualized for the status quo and for two enhanced HHC strategies: 1) active tuberculosis detection only and 2) active tuberculosis detection and LTBI investigation and treatment. In both studies, at the evaluation phase, knowledge gaps among all interviewee groups were observed, and although many contacts were identified, few started LTBI treatment. Following the implementation of solutions, the number of contacts initiating treatment per 100 TB patients increased by 10 [95% confidence interval (CI): -11, 30] in the first study, compared to 44 (95%CI: 26, 61), in the second study. In our economic evaluation, we found that for an enhanced HHC management cascade-of-care, the costs to have one additional HHC to complete LTBI treatment would be half of those to find one additional active TB patient (united states dollars,158.6 vs USD 299.7). Considering the current epidemiologic TB situation in Brazil, the enhanced HHC management that would include LTBI investigation beyond active TB case finding would result in 4,001 averted cases utilizing 12% of the Brazilian TB budget. A public health approach with standardized evaluation, local decisions for improvements, followed by intensive initial and in-service training appears promising to scale up LTBI management.

Tuberculosis infection among primary health care workers / Infecção por tuberculose entre profissionais de saúde da atenção básica

ABSTRACT Objective: To estimate the prevalence of and determine the risk factors associated with latent Mycobacterium tuberculosis infection (LTBI) among primary health care workers in the city of Vitória, Brazil. Methods: This was a cross-sectional study with data collected through a survey regarding socio-demographic, occupational, clinical, and exposure characteristics, as well as knowledge about tuberculosis, conducted between 2011 and 2012. All participants underwent a tuberculin skin test (TST), and TSTs were read at 72 h by a trained professional. Results: A total of 218 primary health care workers participated in the study. The prevalence of TST positivity at the ≥ 10-mm and ≥ 5-mm cut-off points was, respectively, 39.4% (95% CI: 32.9-45.9) and 54.1% (95% CI: 47.4-60.7). Regarding occupational categories, community health agents had the highest proportion of TST positivity, regardless of the cut-off point (≥ 10 mm: 47.5%; and ≥ 5 mm: 60.5%). Regarding factors associated with TST results, "having had a previous TST" showed a statistically significant association with TST positivity at the ≥ 10-mm and ≥ 5-mm cut-off points (OR = 2.5 [95% CI: 1.17-5.30] and OR = 2.18 [95% CI: 1.23-3.87], respectively). Conclusions: The prevalence of LTBI was found to be high among the primary health care workers in this sample. Therefore, we recommend the establishment of a periodic screening program for LTBI and implementation of effective biosafety policies for the prevention of this infection among primary health care workers.

RESUMO Objetivo: Estimar a prevalência de infecção latente pelo Mycobacterium tuberculosis (ILTB) e identificar os fatores de risco associados a essa infecção entre profissionais de saúde da atenção básica no município de Vitória (ES). Métodos: Estudo transversal cujas informações foram obtidas por meio de inquérito sobre dados sociodemográficos, ocupacionais, clínicos, de exposição e de conhecimento sobre tuberculose, realizado entre 2011 e 2012. Todos os participantes foram submetidos ao teste tuberculínico (TT), e a leitura do resultado foi realizada após 72 h por um profissional capacitado. Resultados: Participaram do estudo 218 profissionais de saúde. A prevalência de positividade ao TT foi de 39,4% (IC95%: 32,9-45,9) e de 54,1% (IC95%: 47,4-60,7), respectivamente, para os pontos de corte do TT ≥ 10 mm e ≥ 5 mm. Em relação às categorias profissionais, os agentes comunitários de saúde apresentaram a maior proporção de positividade ao teste, independentemente do ponto de corte considerado (≥ 10 mm: 47,5%; e ≥ 5 mm: 60,5%). Em relação aos fatores associados ao resultado do teste, "ter feito TT anteriormente" apresentou associações estatisticamente significativas com o resultado positivo ao TT para os pontos de corte ≥ 10 mm e ≥ 5 mm [OR = 2,5 (IC95%: 1,17-5,30) e OR = 2,18 (IC95%: 1,23-3,87), respectivamente]. Conclusões: Os profissionais de saúde da atenção básica dessa amostra apresentaram uma alta prevalência de ILTB. Logo, recomendam-se a instituição de um programa de triagem periódica para ILTB e a implantação de políticas efetivas de biossegurança para a prevenção dessa infecção nos profissionais de saúde na atenção básica.

Latent tuberculosis infection screening in juvenile idiopathic arthritis patients preceding anti-TNF therapy in a tuberculosis high-risk country / Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti-TNF em um país de alto risco para tuberculose

Abstract Objectives: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. Methods: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. Results: Sixty-nine JIA patients with current age of 17.4 ± 5.8 years, mean disease duration of 5.0 ± 4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). Conclusion: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients.

Resumo Objetivo: Avaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF. Métodos: Trata-se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti-TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti-TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses. Resultados: Incluíram-se 69 pacientes com AIJ com idade atual de 17,4 ± 5,8 anos, com média de duração da doença de 5 ± 4,9 anos; 47 pacientes receberam um único anti-TNF, enquanto 22 foram transferidos para outro anti-TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos). Conclusão: A avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti-TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.

Latent tuberculosis among professionals from a referral hospital in oncology

Introduction: Tuberculosis (TB) is an ancient contagious disease, and continues to be the leading cause of morbidity and mortality among infectious contagious diseases. It can be considered an occupational infectious disease when it happens in health professionals. These professionals are directly exposed to TB and are considered to be a high risk population for latent tuberculosis infection (LTBI) and active TB. The primary aim of this study was to estimate the prevalence of LTBI among the clinical and administrative staff of an oncology referral hospital in Rio Grande do Sul. The secondary aim of this study was evaluate tuberculin skin test (TST) conversion rate and the risk factors for TST positivity in this population. Methods: A cross-sectional study was carried out in a retrospective cohort with data collected in March 2013 and March 2014. Data of professionals from different hospital units were included. Those with induration ≥ 10 mm were considered as reactors, and conversion rate was assessed by an increase ≥ 10 mm in induration in the second TST compared with the first one. Results: Among the 225 professionals evaluated in 2013, 135 (60%) were reactors and 90 (40%) were non-reactors. The mean age was 32.9 (± 9.55), 176 (78.22%) were female, and most of the reactors worked in the hospital for 4 years or less. Non-reactors in 2013 were recommended to repeat the test in 2014, and the conversion rate was 9.37%. There was no significant difference in prevalence among the different professional categories, and the assessed risk factors were not associated with ILTB. Conclusions: The prevalence of LTBI in the study population was high, reinforcing the need to implement effective control measures to prevent LTBI in the hospital where the study was conducted (AU)

Tuberculosis contact tracing among children and adolescent referred to children's hospital in Rio de Janeiro, Brazil

Objective: To describe the investigation of latent tuberculosis infection and indication for isoniazid preventive therapy in children and adolescents evaluated at the children's hospital. Methods: This retrospective study examines all latent tuberculosis infection subjects with indication for isoniazid preventive therapy attended during 2002-2009 at the pulmonology outpatient clinic from children's hospital in Rio de Janeiro, Brazil. The subjects were classified into three groups by origin: (G1) primary and secondary health units; (G2) children's hospital-pulmonology outpatient clinic; and (G3) children's hospital-specialty outpatient clinics. The association between the variables examined and G1 was analyzed using uni- variate analysis. Results: Of the 286 latent tuberculosis infection cases included 169 (59.1%) were from G1, 56 (19.6%) from G2, and 61 (21.3%) from G3. Latent tuberculosis infection diagnosis without isoniazid preventive therapy prescription was present in 142 (49.6%) cases before arrival at the pulmonology outpatient clinic: 135 (95.1%) from G1, three (2.1%) from G2, and four (2.8%) from G3. Variables associated with G1 were presence of isoniazid preventive therapy criteria before attending the pulmonology outpatient clinic (OR: 62.3; 26.6-146.2), negative HIV infection status (OR: 9.44; 1.16-76.3); contact with pulmonary tuberculosis (OR: 5.57; 1.99-15.5), and residing in Rio de Janeiro city (OR: 1.89; 1.04-3.44). Conclusion: Strategies that increase latent tuberculosis infection identification and isoniazid preventive therapy prescription in primary and secondary health units are urgently needed. .