ABSTRACT
Tuberculosis (TB) remains a serious public health burden worldwide. TB is an infectious disease caused by the Mycobacterium tuberculosis Complex. Innate immune response is critical for controlling mycobacterial infection. NOD-like receptor pyrin domain containing 3/ absent in melanoma 2 (NLRP3/AIM2) inflammasomes are suggested to play an important role in TB. NLRP3/AIM2 mediate the release of pro-inflammatory cytokines IL-1ß and IL-18 to control M. tuberculosis infection. Variants of genes involved in inflammasomes may contribute to elucidation of host immune responses to TB infection. The present study evaluated single-nucleotide variants (SNVs) in inflammasome genes AIM2 (rs1103577), CARD8 (rs2009373), and CTSB (rs1692816) in 401 patients with pulmonary TB (PTB), 133 patients with extrapulmonary TB (EPTB), and 366 healthy control (HC) subjects with no history of TB residing in the Amazonas state. Quantitative Real Time PCR was performed for allelic discrimination. The SNV of AIM2 (rs1103577) is associated with protection for PTB (padj: 0.033, ORadj: 0.69, 95% CI: 0.49-0.97). CTSB (rs1692816) is associated with reduced risk for EPTB when compared with PTB (padj: 0.034, ORadj: 0.50, 95% CI: 0.27-0.94). Serum IL-1ß concentrations were higher in patients with PTB than those in HCs (p = 0,0003). The SNV rs1103577 of AIM2 appeared to influence IL-1ß release. In a dominant model, individuals with the CC genotype (mean 3.78 ± SD 0.81) appeared to have a higher level of IL-1ß compared to carriers of the T allele (mean 3.45 ± SD 0.84) among the patients with PTB (p = 0,0040). We found that SNVs of AIM2 and CTSB were associated with TB, and the mechanisms involved in this process require further study.
Subject(s)
DNA-Binding Proteins/genetics , Disease Resistance/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Tuberculosis/etiology , Alleles , Brazil , CARD Signaling Adaptor Proteins/genetics , Case-Control Studies , Cytokines/metabolism , Female , Genotype , Humans , Male , Mycobacterium tuberculosis , Odds RatioABSTRACT
BACKGROUND: Pulmonary mycoses resemble clinically and radiologically chronic pulmonary tuberculosis. Studies describing the prevalence, etiology and clinical features of pulmonary mycosis are of crucial importance in the Brazilian Amazon. AIMS: To estimate the frequency of pulmonary mycoses in smear-negative tuberculosis patients; to describe their demographic, epidemiological, and clinical characteristics; and to evaluate diagnostic methods. METHODS: A cross-sectional study was conducted at two tuberculosis reference institutions in Amazonas, Brazil. We included 213 patients and collected clinical data, blood and induced sputum to perform serological, direct microscopy, microbiologic culture and PCR-based assays to identify infections caused by Aspergillus fumigatus, Paracoccidioides brasiliensis, Histoplasma capsulatum, Cryptococcus, and HIV. Chest computed tomography was also performed. RESULTS: Pulmonary mycoses were diagnosed in 7% (15/213) of the cases, comprising ten aspergillosis cases, three cases of paracoccidioidomycosis and one case each of histoplasmosis and cryptococcosis. Among the patients with pulmonary mycoses, 86.7% were former tuberculosis patients. The most significant clinical characteristics associated with pulmonary mycoses were cavity-shaped lung injuries, prolonged chronic cough and hemoptysis. CONCLUSIONS: Our study confirmed the high prevalence of pulmonary mycoses in smear-negative tuberculosis patients in the Brazilian Amazon.
Subject(s)
Mycoses , Tuberculosis , Brazil/epidemiology , Cross-Sectional Studies , Humans , PrevalenceABSTRACT
The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.
Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Pulmonary/diagnosis , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Adult , Fatal Outcome , Humans , Male , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Young AdultABSTRACT
The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.
O surgimento de resistência múltipla às drogas de primeira linha implica na utilização de fármacos de maior custo, com duração mais longa, maior complexidade e mais efeitos colaterais. Relatamos os casos de três pacientes com multirresistência primária aos tuberculostáticos. O portador de HIV evoluiu para óbito antes do resultado do teste de sensibilidade. Portanto, o diagnóstico precoce de tuberculose multirresistente e o tratamento adequado devem ser prioridades do Programa Nacional do Controle da Tuberculose, visando interromper a cadeia de transmissão. Além disto, é urgente que seja avaliada a substituição do método das proporções por técnicas mais modernas e mais rápidas.
Subject(s)
Adult , Humans , Male , Young Adult , Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Pulmonary/diagnosis , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Fatal Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapyABSTRACT
O estudo procurou identificar os fatores de risco para o abandono de tratamento da tuberculose no cenário da atenção básica de saúde e avaliar a influência da distância entre o local de atendimento e a residência dos pacientes no abandono do tratamento. Realizou-se um estudo caso-controle com casos novos de tuberculose, tratados no período de 2006 a 2008, nos municípios de Manaus (AM) e Fortaleza (CE). Foram entrevistados 434 indivíduos (92 casos e 342 controles) com questionário estruturado pré-codificado. Estudaram-se os fatores: sexo, anos de estudo, renda, classe econômica, distância entre a unidade de atendimento e a residência, uso de drogas ilícitas, alcoolismo, tabagismo, hospitalização e infecção por vírus da imunodeficiência humana (HIV). O uso de drogas ilícitas apresentou a mais forte associação (risco 2,5 vezes maior), seguido de mais baixa classe econômica e ser do sexo masculino. A construção parcimoniosa do modelo utilizado permitiu identificar que ainda permanecem, como principais fatores de risco, aqueles que representam situações críticas como a drogadição. A situação econômica parece ter importância, não obstante a adoção de tratamento gratuito e universalizado. A condição de ser do sexo masculino permaneceu associada ao abandono, mesmo quando retirado o efeito dos demais cofatores. Avaliou-se a distância entre a residência do paciente e o serviço de saúde e não foi detectada diferença significativa dessas distâncias para casos e controles.
