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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-02062023-150104
Document
Author
Full name
Victor Augusto Camarinha de Castro Lima
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Costa, Silvia Figueiredo (President)
Santos, Daniel Wagner de Castro Lima
Perdigão Neto, Lauro Vieira
Silva, Vinícius Ponzio da
Title in Portuguese
Infecção latente por Mycobacterium tuberculosis em transplante de células tronco hematopoiéticas
Keywords in Portuguese
Diagnóstico
Infecção latente
Mycobacterium tuberculosis
Transplante
Transplante de células-tronco hematopoéticas
Tuberculose
Abstract in Portuguese
INTRODUÇÃO: Há indicação de rastreio de infecção latente por Mycobacterium tuberculosis (ILTB) em candidatos a transplante de células tronco hematopoiéticas (TCTH), devido ao maior risco de reativação de tuberculose. Dois métodos são recomendados para o rastreio: teste cutâneo tuberculínico (TCT) e interferon-gamma release assay (IGRA). O objetivo deste estudo foi avaliar a prevalência de ILTB em candidatos a TCTH, utilizando TCT e o IGRA QuantiFERON-TB Gold PlusÒ (QFTG-Plus), comparando ambos, descrever as características da população com ILTB e a frequência de reativação de tuberculose após o transplante. MÉTODOS: Foram incluídos adultos acompanhados no ambulatório de TCTH, candidatos ao transplante. Os indivíduos foram submetidos a avaliação clínica e entrevista epidemiológica e encaminhados para realizar TCT e QFTG-Plus antes do transplante. O critério para diagnóstico de ILTB foi: ter TCT ou QFTG-Plus positivo ou critério epidemiológico, na ausência de sinais clínicos e radiológicos de doença TB em atividade. Os indivíduos com ILTB tiveram indicação de tratamento com isoniazida. Indivíduos submetidos a TCTH foram seguidos por 12 meses após o transplante. RESULTADOS: Dos 221 indivíduos incluídos, 10 foram excluídos e 211 analisados. Destes, 153 (72,5%) realizaram TCTH: 115 autólogos (75,2%) e 38 alogênicos (24,8%). Foi observada maior frequência do sexo masculino (58,8%) e mediana de idade de 49,0 (intervalo interquartil [IIQ]: 33,0-49,0) anos. A indicação de TCTH autólogo mais frequente foi mieloma múltiplo (44,3%) e de alogênico foi leucemia mieloide aguda (26,3%). Entre os 159 candidatos a TCTH que realizaram QFTG-Plus, 16 tiveram resultado positivo (10,1%); 180 candidatos (85,3%) realizaram TCT, 26 com resultado ³ 5 mm (14,4%). Foi observada uma concordância moderada entre TCT e QFTG-Plus (k = 0,426 [intervalo de confiança 95%: 0,193-0,658]), considerando os 122 indivíduos que realizaram ambos os testes. Foi observada uma prevalência de ILTB de 17,1% (n = 36). Os indivíduos com ILTB eram mais velhos (55,5 [IIQ: 40,0-61,8] versus 47,0 [IIQ: 31,0-58,0] anos, p = 0,038) e tinham uma frequência maior de contato com TB (38,9% versus 6,9%), com risco relativo = 4,36 (intervalo de confiança 95% [IC 95%]: 2,16-8,83), p < 0,001. Na análise multivariada utilizando regressão logística a única variável que teve associação estatisticamente significante com ILTB entre candidatos a TCTH foi contato prévio com TB (odds-ratio: 7,94 [IC 95%: 3,10-20,32], p < 0,001). Entre indivíduos submetidos a TCTH, 26 tiveram diagnóstico de ILTB (17,0%), 22 iniciaram o tratamento com isoniazida, seis (13,6%) apresentaram algum evento adverso e um (3,8%) trocou o esquema, por conta de pancreatite. Dos 109 indivíduos submetidos a TCTH que foram analisados com 12 meses de seguimento, 27 (24,8%) evoluíram a óbito e nenhum caso de reativação de tuberculose foi diagnosticado, em uma mediana de 387,0 (IIQ: 224,0-676,0) dias após o transplante. CONCLUSÕES: Foi observada uma alta prevalência de ILTB em candidatos a TCTH. A frequência de positividade do TCT foi maior que a do QFTG-Plus e a concordância entre os métodos foi fraca. Indivíduos com ILTB tiveram uma maior frequência de contato com TB. Reativação de TB não foi observada durante o seguimento
Title in English
Latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation
Keywords in English
Diagnosis
Hematopoietic stem cell transplantation
Latent infection
Mycobacterium tuberculosis
Transplantation
Tuberculosis
Abstract in English
INTRODUCTION: Screening for latent Mycobacterium tuberculosis (LTBI) infection is indicated for hematopoietic stem cell transplantation (HSCT) candidates, due to the higher risk of tuberculosis reactivation. There are two methods recommended for screening: tuberculin skin test (TST) and interferongamma release assay (IGRA). The aim of this study was to evaluate LTBI prevalence among HSCT candidates, using TST and QuantiFERON-TB Gold PlusÒ (QFTG-Plus) assay, comparing both, to describe the characteristics of LTBI population and the frequency of tuberculosis reactivation after transplantation. METHODS: Adults transplant candidates, followed at HSCT outpatient clinics were enrolled, submitted to clinical and epidemiological evaluation and referred to perform TST and QFTG-Plus before transplantation. LTBI was diagnosed when an individual had a positive TST or QFTG-Plus test or had epidemiological criteria, in the absence of clinical and radiological signs of active TB disease. Treatment with isoniazid was indicated to individuals diagnosed with LTBI. HSCT recipients were followed by 12 months after transplantation. RESULTS: Among 221 enrolled individuals, 10 were excluded and 211 were analyzed. Of them, 153 (72.5%) underwent HSCT: 115 autologous (75.2%) and 38 allogeneic (24.8%). There was a higher frequency of male individuals (58.8%), and the median age was 49.0 (interquartile range [IQR]: 33.0-49.0) years. The most frequent HSCT indication in autologous transplants was multiple myeloma (44.3%), whereas in allogeneic was acute myeloid leukemia (26.3%). Among 159 HSCT candidates who performed QFTG-Plus, 16 had a positive result (10.1%); 180 candidates (85.3%) performed TST and 26 had a result ³ 5 mm (14.4%). A moderate agreement was observed between TST and QFTG-Plus (k = 0.426 [95% confidence interval: 0.193-0.658]), considering 122 individual who performed both tests. The prevalence of LBTI was 17.1% (n = 36). Individuals with LTBI were older (55.5 [IQR: 40.0-61.8] versus 47.0 [31.0-58.0] years, p = 0.038) and had a higher frequency of previous contact with tuberculosis (38.9% versus 6.9%) relative risk = 4.36 (95% confidence interval [CI 95%]: 2.16-8.83), p < 0.001). On multivariate analysis using logistic regression, previous contact with tuberculosis was the only statistically significant association with LTBI (odds-ratio: 7.94 [IC 95%: 3.10-20.32], p < 0.001). Twenty-six HSCT recipients were diagnosed with LTBI (17.0%), 22 were treated, all of them started treatment with isoniazid monotherapy, six (13.6%) had any adverse event and one (3.8%) had to change the scheme to rifampin monotherapy, because of pancreatitis. Among 109 HSCT recipients who were evaluated on 12 months follow-up analysis, 27 (24.8%) died and no cases of tuberculosis reactivation was diagnosed, in a median of 387.0 (IQR: 224.0-676.0) days after transplantation. CONCLUSIONS: It was observed a high LTBI prevalence in HSCT candidates. The TST positivity rate was higher than QFTG-Plus, and the agreement between methods was moderate. LTBI individuals had a higher frequency of previous contact with tuberculosis. Tuberculosis reactivation was not observed during post-transplantation follow-up
 
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Publishing Date
2023-06-06
 
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