Efeito protetivo em longo prazo do tratamento preventivo da tuberculose em uma região de moderada/alta incidência
Efeito protetivo em longo prazo do tratamento preventivo da tuberculose em uma região de moderada/alta incidência
Data
2023
Autores
Teixeira, Leidy Anne Alves
Journal Title
Journal ISSN
Volume Title
Publisher
Instituto Nacional de Cardiologia
Resumo
O tratamento preventivo da tuberculose representa uma das principais estratégias para conter a propagação dessa doença em escala global. No entanto, existem diferentes recomendações de tratamento, dependendo das populações-alvo e das incidências das regiões. A eficácia sustentada do tratamento preventivo da tuberculose em populações que vivem com HIV é um tema mais debatido, enquanto sua aplicação em outros grupos de alto risco, como contatos próximos de pessoas com tuberculose pulmonar, ainda é pouco explorada. O objetivo deste estudo foi o de analisar a duração do efeito protetivo em longo prazo do tratamento preventivo em uma região com incidência moderada/alta de tuberculose. A amostra utilizada neste estudo foi baseada em dois ensaios clínicos randomizados multicêntricos que investigaram regimes terapêuticos de nove meses de isoniazida e quatro meses de rifampicina, essencialmente em contatos de pessoas com tuberculose pulmonar. O recrutamento ocorreu na cidade do Rio de Janeiro, caracterizada por uma incidência moderada/alta de tuberculose (93/100.000 habitantes, ou 0,93/1000 por 1000 pessoas por ano - ppa). Foi realizada consulta ao Sistema de Informação de Agravos de Notificação (Sinan) para identificar os participantes brasileiros que desenvolveram tuberculose (pulmonar ou extrapulmonar) após a randomização por um período de até 12 anos. Calculou-se as taxas de incidência por 1000 ppa de tuberculose entre aqueles que não completaram e os que completaram o tratamento preventivo e, também, as taxas correspondentes aos regimes, estratificadas por períodos: os primeiros 28 meses, após 28 meses e período integral (de zero a 143 meses). Utilizou-se a função falha, ou seja, a probabilidade acumulada de falha, para se calcular a razão dos riscos (Hazard Ratio – HR) da ocorrência dos casos de tuberculose ao longo do tempo considerando os cenários de completude do tratamento e dos regimes. O teste de log-rank foi utilizado para verificar se havia diferença estatística entre as curvas. O resultado da taxa de incidência de tuberculose foi maior nos primeiros 28 meses entre aqueles que não completaram o TPT [6,69/1000 ppa [Intervalo de Confiança (IC) 95%: 2,17; 15,62)] em comparação ao período após os 28 meses [1,74/1000 ppa (IC 95%: 0,47; 4,45)]. Houve 16 casos de tuberculose, dos quais metade ocorreu nos 28 primeiros meses após a randomização. Houve maior proteção pelo tratamento completo (teste de log-rank p=0,042) neste período quando comparado ao tratamento incompleto. Estes resultados sugerem que não há risco
aumentado de tuberculose até 12 anos após um curso de TPT em contatos que vivem em uma área de moderada∕ alta incidência de tuberculose, e que, portanto, neste cenário, não há evidência de que haja necessidade de retratamento com TPT.
Palavras-chave: Mycobacterium tuberculosis, isoniazida, rifampicina, infecção por tuberculose, proteção a longo prazo.
Preventive treatment of tuberculosis represents one of the main strategies to contain the spread of this disease on a global scale. However, there are different treatment recommendations depending on the target populations and incidence rates in the regions. The sustained effectiveness of preventive tuberculosis treatment in populations living with HIV is a more debated topic, while its application in other high-risk groups, such as close contacts of people with pulmonary tuberculosis, is still little explored. The objective of this study was to analyze the duration of the long-term protective effect of preventive treatment in a region with a moderate/high incidence of tuberculosis. The sample used in this study was based on two multicenter randomized clinical trials that investigated therapeutic regimens of nine months of isoniazid and four months of rifampicin, essentially in contacts of people with pulmonary tuberculosis. Recruitment took place in the city of Rio de Janeiro, characterized by a moderate/high incidence of tuberculosis (93/100,000 inhabitants, or 0.93/1000 per 1000 people per year - ppa). The Notifiable Diseases Information System (Sinan) was consulted to identify Brazilian participants who developed tuberculosis (pulmonary or extrapulmonary) after randomization for a period of up to 12 years. The incidence rates per 1000 ppa of tuberculosis were calculated among those who did not complete and those who completed preventive treatment, and also the rates corresponding to the regimens, stratified by periods: the first 28 months, after 28 months and full period (from zero to 143 months). The failure function, that is, the accumulated probability of failure, was used to calculate the risk ratio (Hazard Ratio – HR) of the occurrence of tuberculosis cases over time considering the scenarios of completeness of treatment and regimens. The log-rank test was used to check whether there was a statistical difference between the curves. The tuberculosis incidence rate result was higher in the first 28 months among those who did not complete the TPT [6.69/1000 ppa [95% Confidence Interval (CI): 2.17; 15.62)] compared to the period after 28 months [1.74/1000 ppa (95% CI: 0.47; 4.45)]. There were 16 cases of tuberculosis, half of which occurred within the first 28 months after randomization. There was greater protection due to complete treatment (log-rank test p=0.042) in this period when compared to incomplete treatment. These results suggest that there is no increased risk of tuberculosis up to 12 years after a course of TPT in contacts living in an area of moderate∕ high incidence of tuberculosis, and that therefore, in this setting, there is no evidence that there is a need for retreatment. with TPT. Keywords: Mycobacterium tuberculosis, isoniazid, rifampicin, infection tuberculosis, long term protection.
Preventive treatment of tuberculosis represents one of the main strategies to contain the spread of this disease on a global scale. However, there are different treatment recommendations depending on the target populations and incidence rates in the regions. The sustained effectiveness of preventive tuberculosis treatment in populations living with HIV is a more debated topic, while its application in other high-risk groups, such as close contacts of people with pulmonary tuberculosis, is still little explored. The objective of this study was to analyze the duration of the long-term protective effect of preventive treatment in a region with a moderate/high incidence of tuberculosis. The sample used in this study was based on two multicenter randomized clinical trials that investigated therapeutic regimens of nine months of isoniazid and four months of rifampicin, essentially in contacts of people with pulmonary tuberculosis. Recruitment took place in the city of Rio de Janeiro, characterized by a moderate/high incidence of tuberculosis (93/100,000 inhabitants, or 0.93/1000 per 1000 people per year - ppa). The Notifiable Diseases Information System (Sinan) was consulted to identify Brazilian participants who developed tuberculosis (pulmonary or extrapulmonary) after randomization for a period of up to 12 years. The incidence rates per 1000 ppa of tuberculosis were calculated among those who did not complete and those who completed preventive treatment, and also the rates corresponding to the regimens, stratified by periods: the first 28 months, after 28 months and full period (from zero to 143 months). The failure function, that is, the accumulated probability of failure, was used to calculate the risk ratio (Hazard Ratio – HR) of the occurrence of tuberculosis cases over time considering the scenarios of completeness of treatment and regimens. The log-rank test was used to check whether there was a statistical difference between the curves. The tuberculosis incidence rate result was higher in the first 28 months among those who did not complete the TPT [6.69/1000 ppa [95% Confidence Interval (CI): 2.17; 15.62)] compared to the period after 28 months [1.74/1000 ppa (95% CI: 0.47; 4.45)]. There were 16 cases of tuberculosis, half of which occurred within the first 28 months after randomization. There was greater protection due to complete treatment (log-rank test p=0.042) in this period when compared to incomplete treatment. These results suggest that there is no increased risk of tuberculosis up to 12 years after a course of TPT in contacts living in an area of moderate∕ high incidence of tuberculosis, and that therefore, in this setting, there is no evidence that there is a need for retreatment. with TPT. Keywords: Mycobacterium tuberculosis, isoniazid, rifampicin, infection tuberculosis, long term protection.
Description
Palavras-chave
Isoniazida, Rifampicina, Infecção por tuberculose, Proteção a longo prazo, Mycobacterium tuberculosis, Isoniazid, Rifampicin, Infection tuberculosis, Long term protection
Citação
Teixeira LAA. Efeito protetivo em longo prazo do tratamento preventivo da tuberculose em uma região de moderada/alta incidência. Rio de Janeiro. Dissertação [Mestrado Profissional em Avaliação de Tecnologias em Saúde] Instituto Nacional de Cardiologia - INC; 2023.