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OBJECTIVE: To describe the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) and factors associated with its transmission in Singapore. METHODS: Spoligotyping, 24-loci mycobacterial interspersed repetitive units - variable number of tandem repeats (MIRU-VNTR) typing and demographic data from the national TB notification registry of MTBC culture-positive cases notified from January 2011 to December 2017 were analysed. RESULTS: Of the 12,046 culture-positive cases notified, complete spoligotyping and MIRU-VNTR typing results were available for 8690 (72.1%) belonging to 4950 (57.0%) local-born and 3740 (43.0%) foreign-born persons. From these, 4810 (55.3%) were identified in 883 clusters. The proportion of recent transmission was 45.2%. The East-Asian Lineage 2 accounted for 4045 (47.1%) of isolates, and disproportionately accounted for large clusters. Clustered cases were more likely to be older than 50 years, male, Malay, local-born, Singapore citizens or Permanent Residents, of lower socioeconomic status, imprisoned; to harbour East-Asian Lineage 2 strain; to have cavitary pulmonary TB, positive sputum smear or be recalcitrant treatment defaulters. They were less likely to have multidrug-resistant, or isoniazid or rifampicin mono-resistant TB. CONCLUSION: We demonstrated the diversity of MTBC strains and, notwithstanding the likely over-estimation of clustering using these genotyping methods, elucidated factors associated with TB transmission in Singapore.
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Mycobacterium tuberculosis , Tuberculose Pulmonar , Genótipo , Humanos , Masculino , Repetições Minissatélites , Epidemiologia Molecular , Mycobacterium tuberculosis/genética , Singapura/epidemiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologiaRESUMO
BACKGROUND: Little is known about the joint associations of multiple lifestyle risk factors including smoking, low body mass index, physical inactivity, alcohol consumption, and low diet quality with risk of active tuberculosis. METHODS: We analyzed data from the Singapore Chinese Health Study, a prospective cohort study of 63 257 Chinese adults aged 45-74 years enrolled between 1993 and 1998. Incident cases of active tuberculosis were identified via linkage with the National TB Registry through 31 December 2016. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) of tuberculosis risk in relation to the combined scores of lifestyle risk factors. RESULTS: Compared with participants with none of the risk factors, the adjusted HRs (95% CI) of active tuberculosis for participants with 1, 2, 3, 4, and 5 risk factors were 1.24 (1.02-1.51), 1.84 (1.51-2.23), 2.52 (2.03-3.14), 4.07 (3.07-5.41), and 9.04 (5.44-15.02), respectively (Ptrend < .0001). The HR for those with 5 factors was ~1.5 times the product of individual risk estimates from the 5 factors on a multiplicative scale. The stepwise increase in risk of active tuberculosis with increasing number of lifestyle risk factors was significantly stronger in participants with diabetes than their counterparts without diabetes at recruitment (Pinteraction = .01). CONCLUSIONS: Multiple lifestyle risk factors were associated with risk of active tuberculosis in a synergistic manner. Our findings highlight the importance of public health programs and interventions targeting these factors simultaneously to reduce the tuberculosis burden among the general population.
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Diabetes Mellitus , Tuberculose , Adulto , China/epidemiologia , Humanos , Estilo de Vida , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologia , Tuberculose/epidemiologiaRESUMO
BACKGROUND: Previously treated (ie, recurrent) tuberculosis (TB) cases account for approximately 7%-8% of incident TB globally and in Singapore. Molecular fingerprinting has enabled the differentiation of these patients into relapsed or reinfection cases. METHODS: Patient demographics, disease characteristics, and treatment information were obtained from the national TB notification registry and TB Control Unit. We performed a retrospective, case-control study to evaluate factors associated with recurrent TB disease in Singapore citizens and permanent residents with culture-positive TB from 2006 to 2013 and who developed a second episode of culture-positive TB up to 2016 using multivariable logistic regression analyses. RESULTS: Ninety-one cases with culture-positive first and recurrent TB disease episodes were identified. Recurrent TB was associated with age ≥60 years (adjusted odds ratio [aOR], 1.98 [95% confidence interval {CI}, 1.09-3.61), male sex (aOR, 2.29 [95% CI, 1.22-4.51]), having concomitant pulmonary and extrapulmonary TB (aOR, 3.10 [95% CI, 1.59-6.10]) and extrapulmonary TB alone (aOR, 3.82 [95% CI, 1.12-13.31]), and was less likely in non-Malays (aOR, 0.52 [95% CI, .27-.99]). DNA fingerprinting results for both episodes in 49 cases differentiated these into 28 relapsed and 21 reinfection cases. Relapse was associated with having concomitant pulmonary and extrapulmonary TB (aOR, 9.24 [95% CI, 2.50-42.42]) and positive sputum acid-fast bacilli smear (aOR, 3.95 [95% CI, 1.36-13.10]). CONCLUSIONS: Relapse and reinfection contributed to 57% and 43%, respectively, of recurrent TB in Singapore. Our study highlights the underappreciated association of concomitant pulmonary and extrapulmonary TB as a significant risk factor for disease relapse.
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There were 290 multidrug-resistant (MDR)-TB cases diagnosed in Singapore from 2006 to 2018. Eighty-one percent were foreign-born. Spoligotyping and MIRU-VNTR methods identified 108 patients in 24 clusters. The Beijing spoligotype accounted for 22 clusters. Whole genome sequencing (WGS) analysis reduced the number of clustered patients and clusters to 43 and nine respectively. One MIRU cluster was redefined into three WGS clusters. All the clusters had foreign-born source cases. Forty percent of local-born, versus 9% of foreign-born, MDR-TB cases belonged to WGS clusters. WGS more accurately elucidated potential MDR-TB transmission which was overestimated by conventional genotyping methods in Singapore.
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Antituberculosos/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Farmacorresistência Bacteriana Múltipla , Genótipo , Humanos , Epidemiologia Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Singapura/epidemiologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Although asthma is associated with impaired lung immunity, it is unclear whether asthma affects the risk of active tuberculosis (TB). Because the upper and lower airways are immunologically related, sinonasal disease may also modify susceptibility to TB disease. OBJECTIVES: To evaluate whether asthma and sinonasal disease prospectively modulate the risk of active TB in the Singapore Chinese Health Study. METHODS: In this population-based prospective cohort, we recruited 63,257 Chinese adults aged 45 to 74 years from 1993 to 1998 in Singapore, and conducted follow-up I interviews among 52,325 surviving participants from 1999 to 2004. Data on self-reported history of physician-diagnosed sinonasal disease were collected at baseline, and data on asthma and chronic bronchitis were collected at follow-up I interviews. Active TB cases were identified by linkage with the National TB Notification Registry through December 2014. Multivariable Cox proportional hazards regression models were used to estimate the risk of active TB. RESULTS: During a mean follow-up of 17 years from recruitment, there were 1249 cases of active TB, and among them, 678 cases were diagnosed in the 12-year period from follow-up I interviews. We observed reduced risk of active TB in those with a history of asthma at follow-up I (hazard ratio [HR], 0.55; 95% CI, 0.32-0.93) or sinonasal disease at baseline (HR, 0.59; 95% CI, 0.36-0.95). Conversely, history of chronic bronchitis was not associated with risk of TB (HR, 0.95; 95% CI, 0.68-1.31). CONCLUSIONS: Asthma or sinonasal disease may modulate immunological response to reduce the incidence of active TB in the adult population.
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Asma/epidemiologia , Doenças dos Seios Paranasais/epidemiologia , Tuberculose Pulmonar/epidemiologia , Idoso , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologiaRESUMO
Diagnosing and treating latent tuberculosis (TB) infection (LTBI) is recognized by the World Health Organization as an important strategy to accelerate the decline in global TB and achieve TB elimination. Even among low-TB burden countries that have achieved high rates of detection and successful treatment for active TB, a number of barriers have prevented implementing or expanding LTBI treatment programmes. Of those infected with TB, relatively few will develop active disease and the current diagnostic tests have a low predictive value. LTBI treatment using isoniazid (INH) has low completion rates due to the long duration of therapy and poor tolerability. Both patients and physicians often perceive the risk of toxicity to be greater than the risk of reactivation TB. As a result, LTBI treatment has had a limited or negligible role outside of countries with high resources and low burden of disease. New tools have emerged including the interferon-gamma release assays that more accurately diagnose LTBI, particularly in people vaccinated with Bacillus Calmette-Guerin (BCG). Shorter, better tolerated treatment using rifamycins are proving safe and effective alternatives to INH. While still imperfect, TB prevention using these new diagnostic and treatment tools appear cost effective in modelling studies in the United States and have the potential to improve TB prevention efforts globally. Continued research to understand the host-organism interactions within the spectrum of LTBI is needed to develop better tools. Until then, overcoming the barriers and optimizing our current tools is essential for progressing toward TB elimination.
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Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Rifamicinas/uso terapêutico , Antituberculosos/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Testes de Liberação de Interferon-gama , Isoniazida/efeitos adversos , Tuberculose Latente/epidemiologia , Adesão à Medicação , Teste TuberculínicoAssuntos
Tuberculose , Vitaminas , Antioxidantes , Carotenoides , Estudos de Coortes , Humanos , Estudos ProspectivosRESUMO
Antioxidants may protect against oxidative stress, which is associated with tuberculosis (TB) disease. However, direct evidence for a protective association between dietary antioxidants and TB incidence in humans has been lacking. The relationship between intake of antioxidant vitamins (vitamins A, C, D, and E) and individual carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein) and TB incidence was examined in the Singapore Chinese Health Study, a prospective cohort study of 63,257 adults aged 45-74 years enrolled during 1993-1998. Baseline intake of these antioxidants was estimated using a validated semiquantitative food frequency questionnaire including questions on use of dietary supplements. After an average of 16.9 years of follow-up, 1,186 incident active TB cases were identified among cohort participants. Compared with the lowest quartile, reduced risk of active TB was observed for the highest quartile of vitamin A intake (hazard ratio = 0.71, 95% confidence interval: 0.59, 0.85; P-trend < 0.01) and ß-carotene intake (hazard ratio = 0.76, 95% confidence interval: 0.63, 0.91; P-trend < 0.01), regardless of smoking status. Lower TB risk was seen for vitamin C intake among current smokers only. Other vitamins and carotenoids were not associated with TB risk. These results suggest that vitamin C may reduce TB risk among current smokers by ameliorating oxidative stress, while vitamin A and ß-carotene may have additional antimycobacterial properties.
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Antioxidantes/administração & dosagem , Carotenoides/administração & dosagem , Dieta/estatística & dados numéricos , Micronutrientes/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Tuberculose/prevenção & controle , Idoso , Antioxidantes/fisiologia , Carotenoides/imunologia , Carotenoides/fisiologia , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Micronutrientes/imunologia , Micronutrientes/fisiologia , Pessoa de Meia-Idade , Estresse Oxidativo/imunologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Tuberculose/epidemiologia , Tuberculose/imunologiaAssuntos
Reações Falso-Negativas , Testes de Liberação de Interferon-gama/métodos , Interferon gama/metabolismo , Tuberculose/diagnóstico , Adulto , Estudos Transversais , Feminino , Variação Genética , Humanos , Cooperação Internacional , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Inquéritos e QuestionáriosAssuntos
Antígenos de Bactérias/imunologia , Complicações do Diabetes/microbiologia , Interferon gama/imunologia , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Tuberculose/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Kit de Reagentes para Diagnóstico , Recidiva , Fatores de Risco , Sensibilidade e Especificidade , Singapura , Linfócitos T/citologia , Tuberculose/complicações , Tuberculose/diagnósticoAssuntos
Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico por imagem , Tuberculose Pulmonar/diagnóstico por imagem , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Prisioneiros , Radiografia , Singapura , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/transmissãoRESUMO
Singapore has experienced a rise in the tuberculosis (TB) incidence rate among her local population since 2008, which we believe, is contributed in no small part to a recent increase in community transmission due to delayed diagnosis of infectious pulmonary TB cases. Data from the TB notification registry showed an increase from 2004 to 2008 in the number and proportion of sputum acid-fast bacilli smear-positive pulmonary TB cases with prolonged cough. Two surveys at the TB Control Unit showed that healthcare system delays exceeded patient delay in seeking medical consultation. There is thus an urgent need to heighten TB awareness among the public and the medical community in order to reduce the time taken to diagnose infectious TB cases in Singapore.
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Controle de Infecções/métodos , Tuberculose Pulmonar/diagnóstico , Diagnóstico Tardio , Humanos , Incidência , Pulmão/diagnóstico por imagem , Radiografia , Encaminhamento e Consulta , Singapura/epidemiologia , Tuberculose Pulmonar/epidemiologiaRESUMO
INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) is an emerging global health risk. We present the first case report of XDR-TB in Singapore. CLINICAL PICTURE: A 41-year-old Indonesian lady with previously treated pulmonary tuberculosis presented with chronic cough. Her sputum was strongly acid-fast bacilli positive and grew Mycobacterium tuberculosis complex resistant to first and second-line TB medications. TREATMENT: She received 5 months of intensive multidrug treatment without sputum smear conversion. She then underwent resection of the diseased lung. The total cost incurred amounted to over S$100,000. OUTCOME: She achieved sputum smear/culture conversion post-surgery, but will require further medical therapy for at least 18 months. CONCLUSION: XDRTB is poorly responsive to therapy and extremely expensive to manage. Its prevention by strict compliance to therapy is paramount.