Alcohol abuse and smoking Important risk factors for TB? 18 th Swiss Symposium on tuberculosis Swiss Lung Association 26 Mach 2009 Knut Lönnroth Stop TB Department WHO, Geneva
Full implementation of Global Plan: TB not eliminated by 2050 10000 Propects for TB elimination by 2050 Incidence Incidence/100,000/yr / 1 million and year 1000 100 10 1 Elimination 16%/yr Global Plan 6%/yr Current trajectory 1%/yr 2000 2010 2020 2030 2040 2050 Year Projected incidence 100x bigger than elimination target in 2050 Elimination target: 1 / million / year by 2050
Population attributable fraction - risk factors for progression to disease HIV infection Malnutrition Diabetes Relative risk for active TB disease 20.6/26.7* 3.2** 3.1 Weighted prevalence (22 HBCs) 1.1% 16.5% 3.4% P RR 1 PAF P RR 1 1 Population Attributable Fraction 19% 27% 6% Alcohol use (>40g / d) Active smoking Indoor Air Pollution 2.9 2.6 1.5 7.9% 18.2% 71.1% 13% 23% 26% Sources: Lönnroth K, Raviglione M. Global Epidemiology of Tuberculosis: Prospects for Control. Semin Respir Crit Care Med 2008; 29: 481-491. *Updated data in GTR 2009. RR=26.7 used for countries with HIV <1%. **Updated data from Lönnroth et al. A consistent log-linear relationship between tuberculosis incidence and body-mass index. Submitted, 2009
Alcohol use and TB: Background 1. High prevalence of alcohol use disorders among TB patients: 10-50% of TB patients are alcoholics in Canada, Australia, USA, Switzerland, Russia 2. High TB risk among persons with alcohol use disorders: 10-50 times higher incidence of TB among social welfare receivers with drug use problems, people living in shelters for drug users, and homeless 3. Causal link or confounded by socioeconomic status, living condition, smoking, etc?
Alcohol use as a risk factor for tuberculosis a systematic review. Lönnroth K, Williams BG, Stadlin S, Jaramillo E, Dye C. BMC Public Health 2008; 8: 289
Methods Inclusion criteria Association between active TB disease and either alcohol consumption and/or diagnosis of alcohol use disorder Individual level data (case control and cohort studies) Search Hans Rieder's TB literature collection PubMed Review matrix from systematic review of TB and smoking Reference lists from reviewed articles Included studies 21 studies, of which 18 case control and 3 cohort studies 13 from high-income countries, 4 middle, 4 low Varying definitions of exposure, see below
Crampin Tocque Hemilä Kolappan Results Kim Dong Lienhardt Brown II Buskin Thomas Low exposure: cut-off for intake set at <40 g alcohol / day Shetty Schluger Coker Lewis High exposure: cut off for intake set at >=40g/day, or diagnosed alcohol disorder (dependence, abuse, or "heavy drinking") Moran Rosenman Mori Selassie Spletter Brown I Exposure not clearly defined Tekkel Riekstina 0.1 1 10 100 Odds Ratio
Studies with exposure defined as either alcoholism or high consumption Low exposure level Brown II Buskin Crampin Schluger Lewis Tocque Moran Rosenman Hemilä Mori Selassie Spletter Brown II Brown I 3.5 (2.0-5.9) Riekstina Pooled 1.3 (1.0-1.9) Pooled 0.1 1 10 100 Odds Ratio 0.1 1 10 100 Odds Ratio
Pooled estimates for Highexposure/alcoholism studies Study category Pulmonary TB cases only All types of TB Controlled for HIV status Controlled age, sex, SES, smoking Controlled HIV, age, sex, SES, smoking Controlled infection, age, sex, SES Excluding three smallest studies No of studies 2 6 7 5 4 4 8 Random effect assumption (95% CI) 3.67 (2.58-5.22) 2.87 (1.47-5.58) 3.26 (2.26 4.70) 3.49 (2.06-5.90) 4.08 (2.49 6.68) 4.21 (2.73-6.48) 2.94 (1.89-4.59)
Funnel plot, high exposure studies 0.5 Std. error of log(or) 0.4 0.3 0.2 0.1 0.0-0.5 0.4 0.7 0.0 1 2 0.5 4 7 1.0 10 20 Odds Ratio Points to the right of the dashed line are significant on 5% level Points outside the funnel indicate heterogeneity
Methodological considerations Unclear definition of alcohol use disorders in reviewed papers what does "high exposure" actually correspond to? Misclassification of exposure? (underestimate real risk increase?) Representative studies? (low-income countries, Eastern Europe?) One cohort study, and few recent high-quality studies. Difference between pulmonary TB and other types? Residual confounding?
Possible causal pathways 1. Increased risk of infection Social mixing patterns high risk of exposure: Drinking environment Alcohol related social drift 2. Increased risk of progression to disease Direct effects of alcohol on immunity Indirect effects on immunity of alcohol-related disorders, including malnutrition, malignancies, chronic diseases, etc
Population attributable fraction Regional variations in HBCs Africa AFRICA (8 HBCs) Europe EUROPE (Russia) 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% HIV Malnutrition Diabetes Smoking Indoor air pollution Alcohol abuse 0% HIV Malnutrition Diabetes Smoking Indoor air pollution Alcohol abuse
Attributable fraction TB disease TB disease attributable to alcohol in selected countries (based on RR=2.9 and prevalence of drinking >40g alcohol / d) 60% 50% 40% 30% Men Women 20% 10% 0% Russia Nigeria Thailand South Africa Brazil China India Pakistan
Tobacco and TB Three recent systematic reviews: Slama, K., Chiang, C.Y., Enarson, D., Hassmiller, K., Fanning, A., Gupta, P., et al. Tobacco and tuberculosis: a qualitative systematic review and meta analysis. Int J Tuberc Lung Dis 2007, 11,1049-61 Lin, H., Ezzati, M., & Murray, M. Tobacco smoke, indoor air pollution and tuberculosis: a systematic review and meta-analysis. PLoS Medicine, 2007 4,e142 Bates MN, Khalakdina A, Pai M, Chang L, Lessa F, Smith KR. Risk of tuberculosis from exposure to tobacco smoke: a systematic review and meta-analysis. Arch Intern Med. 2007 Feb 26;167(4):335-42.
Tentative conclusions on evidence: Strong for active smoking and TB disease (RR 2-3) Moderate for passive smoke and TB disease Moderate for relapse Limited for TB infection Limited for mortality
PAR% smoking Our global assessment for 22 HBCs: 23% Jha et al 2008: 38% of TB deaths among men and 9% among women in India Modelling 1: Hassmiller (PhD thesis 2007): 48% of TB cases in India Modelling 2: Lin et al 2008: Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence by 14 52% in China (if 80% DOTS coverage is sustained) Next step: dynamic modelling of global data
Action implications Prevent TB through addressing smoking and alcohol abuse Medical interventions (role of NTPs?) Public health (education, laws, restrictions, etc, role of NTPs) Social medicine (the upstream determinants of smoking and alcohol abuse, role of NTPs?) Screen for TB among smokers and alcoholics Additional research needed Original studies on smoking and alcohol interaction More modelling to understand attributable fraction Intervention studies: evaluate effect of prevention / treatment of alcoholism and smoking